(navigation image)
Home American Libraries | Canadian Libraries | Universal Library | Community Texts | Project Gutenberg | Children's Library | Biodiversity Heritage Library | Additional Collections
Search: Advanced Search
Anonymous User (login or join us)
Upload
See other formats

Full text of "Annual Report of International Activities 1978"

national institutes of health 




annual 
renort of 



mm 



activities 

fiscal year 1978 



U.S. DEPARTMENT OF 

HEALTH, EDUCATION, AND WELFARE 

Public Health Service 

National Institutes of Health 



■^^W- 



U,5' NATIONAL INSTITUTES OF HEALTH 

00 ANNUAL REPORT OF INTERNATIONAL ACTIVITIES5 

FISCAL YEAR 1978 



Prepared by 
John E. Fogarty International Center 

for 
Advanced Study in the Health Sciences 



U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE 

Public Health Service 

National Institutes of Health 

NIH Publication No. 79-1994 
October 1979 



TABLE OF CONTENTS 

Page 

introduction v 

John E. Fogarty International Center for Advanced 

Study in the Health Sciences 1 

Advanced Study Programs 2 

Scientific Meetings 2 

Scientific Memoranda 6 

Research Coordination Projects 7 

Geographic and Policy Studies 9 

Fogarty Scholars-in-Residence 11 

International Fellowship and Exchange Programs 13 

International Research Fellowship Program 13 

Senior International Fellowship Program 14 

International Neurosciences Fellowship Program .... 15 
International Tropical Diseases Research 

Fellowship Program 15 

Other Research Fellowship Activities 15 

Individual Specialist Health Exchange Programs .... 16 

Coordination and Services for NIH International 

Relationships 18 

Bilateral Agreements for Cooperation in Biomedical 

Research 19 

Special Foreign Currency Program 20 

International Visitors Center 29 

The NIH Visiting Program 30 

International Education Program 33 

U.S. Government Support of the Gorgas Memorial 

Laboratory, Panama 34 

International Cooperation by Components of NIH 36 

National Cancer Institute 36 

National Eye Institute 56 

National Heart, Lung, and Blood Institute 61 



III 



National Institute of Aging 82 

National Institute of Allergy and Infectious Diseases 84 

National Institute of Arthritis, Metabolism, and 

Digestive Diseases 101 

National Institute of Child Health and Human 

Development 108 

National Institute of Dental Research 116 

National Institute of Environmental Health Sciences 118 

National Institute of Neurological and Communicative 

Disorders and Stroke 124 

National Library of Medicine 127 



IV 



Introduction 



This is the 10th annual report of the international activities of the 
National Institutes of Health (NIH) published by the John E. Fogarty 
International Center for Advanced Study in the Health Sciences. It is 
a summary, primarily in narrative form, of the highlights of activities 
for fiscal year (FY) 1978 and is supplemented by two companion book- 
lets, NIH Statistical Reference Book of International Activities and NIH 
International Awards for Biomedical Research and Research Training. 

Over the years of its existence, NIH has been involved extensively 
with scientists and NIH counterpart organizations of other countries 
and international organizations in furtherance of its biomedical research 
mission. The principal legislative authority for the conduct of these 
international relationships is contained in Section 307 of the Public 
Health Service Act. International cooperation has made it possible to 
draw upon particular expertise and experience existing in other countries 
in addressing the many health and disease problems faced by the United 
States and the world generally. At the same time, cooperation permits 
U.S. scientists to broaden their horizons through productive contacts 
abroad. To the extent that U.S. and foreign biomedical research efforts 
can be coordinated and resources shared, duplication of effort is avoided 
and research progress enhanced. 

Although we speak in this report of NIH international programs 
and activities, it is very important to emphasize that these international 
efforts include not only those of NIH scientists and physicians but also 
those of universities and research institutions throughout the United 
States and abroad. These latter activities are conducted using extramural 
support mechanisms of NIH and its components via research grants, con- 
tracts, fellowships, etc. As a consequence, the biomedical community at 
large is involved, adding strength to the total research, research training 
and educational capabilities of this and other countries. Through these 
intramural and extramural means, all components of NIH participate 
and share to differing degrees in international activities, depending upon 
their particular needs and missions. 

The Fogarty International Center was established in 1968 for the 
special purpose of fostering a broad and international approach to 
disease problems and issues and of being a focal point at NIH for coor- 
dination of NIH international interests. Its activities, therefore, form the 
first major subdivision of this report. Activities of other Institutes and 



components of NIH which have important international relationships are 
encompassed in the second major subdivision. 

Fiscal Year 1978 was fairly typical among recent years for the 
level and extensiveness of international activity. Economic conditions 
and budget limitations naturally precluded undertaking certain research 
initiatives that would have been desirable. Nevertheless, accomplish- 
ments were significant, as discussed herein. In line with overall Govern- 
ment initiatives in international health, increasing attention was given 
to the potential for mutually valuable relationships with developing 
countries in a number of scientific fields, such as tropical and infectious 
diseases. Impossible of recording, of course, is that large and vital seg- 
ment of international activity which goes on informally directly between 
individual scientists at meetings, during visits, by correspondence or 
through exchanges of biological materials. Such contacts form an essen- 
tial matrix for institutional relationships and in a larger sense are the 
ultimate goal of more formalized international programs, namely, to 
make possible, and open, doors of communication. 

Questions concerning this report and its companion documents 
should be addressed to Dr. Joseph R. Quinn, Chief, International Co- 
operation and Geographic Studies Branch, Fogarty International Center. 

Leon Jacobs, Ph.D. 

Director 

Fogarty International Center 



9rit 



VI 



John E. Fogarty International Center 
for Advanced Study in The Health Sciences 



In recognition of the growing importance of international relation- 
ships for the advancement of biomedical knowledge in seeking solutions 
to the cause, prevention and treatment of disease, the Fogarty Inter- 
national Center (FIC) was established by the Congress in 1968 through 
Public Law 90-557 as a component of NIH. Some of its functions were 
incorporated from the former NIH Office of International Research; 
others were added since its establishment. The Center's name recog- 
nizes the staunch support given to biomedical research by the late 
Congressman John E. Fogarty, who did much to acquaint the public 
and the Congress in the post-World War II era with the importance of 
continuing and long-range support of biomedical research for the ulti- 
mate amelioration and solutions to disease problems. 

The Fogarty International Center serves NIH both as a component 
with its own particular programs, for which it is uniquely suited, and as 
a resource for coordination and services for overall NIH international 
relationships. In these capacities, the Center works closely with other 
units of the NIH scientific complex on many activities where mutual 
interests can be served, where subjects cut across the interests of several 
agencies, or where an issue is of broad concern to NIH as a whole— such 
as the joint sponsorship of conferences. Indeed, most of the activities 
of the Center coincide in one way or another with the specific scien- 
tific interests of one or more of the NIH components and are mutually 
supportive, directly or indirectly. 

The Center interprets its role with respect to "international" in a 
very broad way, not only in the more restricted sense of dealing with 
specific countries and international organizations, but also in terms of 
dealing with significant issues, problems, or research interests which 
transcend national boundaries. It is in this way that the Center feels 
U can best serve both the domestic and international interests of the 
United States and NIH most effectively. 

As detailed in the following sections, the Advanced Study Pro- 
grams and the International Research Fellowship and Exchange Programs 
of the Center are activities which are directly administered, and, in most 
cases, funded by the Center. They may also be jointly sponsored and 
supported together with other NIH Institutes or outside organizations. 
In serving its other role of coordination for NIH 'international relation- 
ships, the Center provides staff guidance, oversight, and support for 



international interests or activities of NIH as a whole whose final imple- 
mentation devolves upon the various components of NIH or other 
organizations. 

U.S. Government support for the Gorgas Memorial Laboratory, 
Panama, through its parent organization, the Gorgas Memorial Institute 
of Tropical and Preventive Medicine, Inc., is also included as an activity 
of the Center. Although the Institute is a private organization, the core 
support for operation and maintenance of the laboratory is provided 
through the budget of the Center. The responsibilities of the Center are 
limited to liaison and general program oversight with respect to these 
funds. 

Finally, because of the scope of these functions and interests, the 
Center is able to serve the Director of NIH, Institute Directors, and 
principal staff as an information and advisory resource on international 
matters. 



Advanced Study Programs 

The Advanced Study Programs form a key part of the concept and 
purpose of the Center, serving as important means for the development 
of biomedical knowledge, acquisition and communication of research 
information, and the consideration of issues related to the applications 
of research to the solution of major health problems. These programs 
draw upon the expertise of U.S. and foreign scientists, administrators, 
and other specialists for the consideration of various topics of current 
relevance, many of which require a multidisciplinary approach or bridge 
the interest of specialties or missions of the categorical Institutes of 
NIH. 



Scientific Meetings 

Conference activity at the Fogarty International Center increased 
in FY 1978 over that of FY 1977 as the Center undertook the manage- 
ment of additional meetings which in the past had been handled by 
individual lead Institutes. Those conference topics that overlapped the 
categorical interests of individual Institutes, e.g., as in diabetes research, 
kidney research, epidemiology, nutrition, toxicology, fundamental 
research in molecular biology and immunology, etc., were reviewed with 
appropriate components of NIH and other Federal agencies. Multiagency 
sponsorship of scientific meetings broadens the participation and scien- 
tific coverage, reduces overlap and duplication of efforts, provides for a 
more extensive scientific review, and spreads the burden of costs. 

In FY 1978 there were a total of 91 proposed meetings of which 
71 were approved. Funds requested for meetings approved by review 
exceeded $1,750,000, of which approximately $1,300,000 was provided. 
Of this total, the Fogarty International Center provided about $500,000, 



the remainder being contributed by other agencies. Seventeen of 
the FY 1978 meetings were held at NIH and 24 took place overseas; 
this was an increase from four at NIH and eight abroad in FY 1977, 

. The number of co-supporting agencies participating in the scien- 
tific review ranged from 2 to 17 per conference, with the average ex- 
ceeding 7. The average cost for a conference held at NIH in FY 1978 
was $26,284. Meetings not held at NIH varied in size and location and 
received an average level of support of $17,223, with a range of $2,000 
to $70,000. For these conferences, support for the individual participant 
was limited to the cost of his or her round-trip transportation at econ- 
omy rates. 

The following meetings were held during FY 1978: 

• National Conference on Clinical Trials Methodology 

Last year there were nearly 800 clinical trials involving NIH. The 
usefulness of such trials, which frequently involve the participation of 
physicians and hospitals in many parts of the country, depends on the 
adherence to a common set of practices and uniform reporting of ob- 
servations and results. The cooperation and degree of interest of the 
medical community in this effort was exemplified by the fact that 700 
professionals came to NIH at their own expense to participate in the 
national conference on clinical trials methodology, managed by FIC and 
sponsored by the NIH Clinical Trials Committee, and 11 of the com- 
ponents of NIH. 

The essential con^nsus that developed at the conference was that 
a considerable body of information on clinical trials methodology is 
available, but adequate mechanisms for exchanging this information do 
not exist. It was proposed that an organization be established which 
would assess the interests of those working in clinical trials, including 
the organization of conferences and the sponsorship of a journal that 
would publish material on clinical trials methodology. 

• Conference on Obesity 

Obesity is one of the major public health problems in the United 
States; it is estimated that between 30 to 50 million Americans are 
overweight. More than 100 experts from the United States and abroad 
gathered at the National Institutes of Health to consider obesity, its 
problems and treatments, and to recommend courses of action. 

Proposals for public action included discussion of ways to better 
inform physicians, as well as members of the public, regarding the 
effects of obesity on health and of means of lifetime weight control. 
The associated increased risks of diabetes, endometrial cancer, stroke, 
high blood pressure, and heart attacks, not to mention the social and 
psychological impairments, were discussed. 

Conferees expressed particular concern regarding the liquid protein 
diet because of the possibility of serious side effects, including depletion 
of potassium. (Subsequently, the Food and Drug Administration im- 



posed limitations on the sale of liquid protein diets.) Labeling of caloric 
and nutritional values of foods was discussed, as well as economic 
rewards for weight loss, such as reduced insurance premiums. 

Priorities for basic and clinical research were agreed upon, and 
publication of the conference proceedings is in progress. 

• The Biomedical and Behavioral Basis of Clinical Nutrition: A 
Projection for the 1980's 

The Nutrition Coordinating Committee of NIH, aided by the 
Fog^rty International Center, sponsored this conference to review 
biomedical and behavioral research in nutrition, to relate this research 
to current clinical practice, and to project the future frontiers of nutri- 
tional investigations and applications. 

The conferees considered as a pressing need the encouragement 
and extension of clinical nutrition research as an essential foundation 
for continued improvement in man's well-being. They specifically cited 
the actions of nutrients on certain key regulatory enzymes that govern 
the disposal of drugs and environmental pollutants, and the different 
roles of saturated and unsaturated fats on the regulation of cholesterol 
and lipoprotein metabolism and the consequences in terms of coronary 
heart disease. 

• The International Workshop on Longevous Population of Vil- 
cabamba, Ecuador 

Vilcabamba was one of three populations renowned for extreme 
longevity and apparent good health in old age; the other two popula- 
tions being the Hunzas of Pakistan and the Georgians of Russia. The 
National Institute on Aging and the Fogarty International Center col- 
laborated in bringing together scientists from six countries who had 
worked in Vilcabamba. 

Prevailing misconceptions about longevity in Vilcabamba were 
dispelled after a careful construction of family genealogies which showed 
that the Vilcabamba "centenarian" would be about 86 years old. The 
initial confusion arose in part from the common custom of giving a sur- 
viving child the same name as a sibling who had died. Also, the practice 
of passing a name from one generation to the next caused confusion in 
recorded birth dates— the birthday of a grandparent being taken as the 
birth date of a parent. Consequently, a person's age was often the sum 
total of more than one family member. 

The real scientific import of Vilcabamba was the unusually healthy 
condition of the elderly who comprised a typical age distribution rela- 
tive to other populations, but whose incidence of atherosclerosis in 
people 80 and over was uncommonly low. 

• Colloquium on Selected Diarrheal Diseases of the Young 

International experts on diarrheal diseases of the young were 
brought together to draft conclusions and recommendations for the con- 
trol and treatment of these diseases, and to disseminate this information 



to the human and veterinary nnedical comnnunities for the public wel- 
fare. Diarrheal diseases of the young are caused by similar pathogens 
whether "the ypung" are calves, piglets, or human babies. In man, 
diarrheal diseases are among the most common diseases experienced, 
second only to upper respiratory tract diseases, and these diseases are 
endemic in most developing countries, constituting a life-threatening 
condition for the newborn. 

One widespread cause of diarrhea in human infants and in young 
animals is the rotavirus. Other common causes of diarrhea include 
parvoviruses (cat distemper), corona viruses, and a variety of bacteria, 
including toxigenic and invasive E. coli. Salmonella, and Cryptoposldia. 
The participants agreed that the newborn succumb to diarrheal diseases, 
not because of the viral or bacterial agent, but more often because of 
the loss of electrolytes and water with consequential dehydration, 
acidosis and shock. Therefore, it was recommended that any program 
developed to control diarrheal diseases must emphasize preventive 
measures and supportive treatment. 

The majority of scientific meetings sponsored and managed by the 
Center were devoted to an analysis of recent research results, interpre- 
tation of such results contributing to the scientific basis for preventive, 
palliative, or curative measures. An area of basic research undergoing 
rapid development, with increasing implications for medicine, is com- 
plex carbohydrates in biological recognition, the subject of a conference 
held in July of 1978. 

• Complex Carbohydrates in Biological Recognition 

Complex carbohydrates play a crucial role in biology by confer- 
ring specificity to structures in which they occur. Their presence is 
manifested in phenomena such as the selective binding of cells 
of enzymes, hormones, and toxins; the immune response; cellular ad- 
hesion; and the control of differentiation and cell growth. This spec- 
ificity results from the recognition of particular carbohydrate sequences 
in glycoproteins or glycolipids by complementary sites on proteins. 
The questions discussed at the conference were how are these specific 
recognition determinants displayed on complex carbohydrates, and how 
do the carbohydrate sensors, after perturbation, transmit specific signals. 

The consensus of the conferees at the meeting was that the field 
of complex carbohydrates in biological recognition is at present in an 
explosive state of development, with increasing implications for medi- 
cine, directly involving diverse areas such as enzyme replacement ther- 
apy, organ transplants, tumor immunology, protection against infectious 
disease and toxins, and novel approaches for targeting of drugs. 

Other conferences of research interest with significant medical 
implications held at NIH in FY 1978: 

• International Symposium on Papovaviruses and Their Role in 
Cell Transformation and Oncogenesis 



• NIH/WHO Workshop on the Ecology of Influenza Viruses 

• Meeting of Committee on Typification of Species of Protozoa 

• International Meeting on Guidelines for Detection of Hepatotox- 
icity Due to Drugs and Chemicals 

• Symposium on Autosomal Dominant Genetic Neurological Dis- 
orders 

During FY 1978 the Center coordinated the limited, partial sup- 
port of international meetings of topical interest to the mission of the 
NIH, which included the following research areas: in vitro induction 
and measurement of antibody synthesis, bacteriology, mycology, bio- 
physics, virology, transplantation, invertebrate pathology, streptococci 
and streptococcal disease, Raman spectroscopy, flavins and flavoproteins, 
mononuclear phagocytes, biological membranes, and leukocyte cultures. 

Domestic meetings not held at NIH, but of programmatiq inter- 
est to the Institutes, in which the Fogarty International Center par- 
ticipated, included conferences on: Transmembrane Signaling; Normal 
and Abnormal Red Cell Membranes; Persistent Viruses; Fast Biochemical 
Reactions in Solution; Bleomycin; Hemoglobin Synthesis; Theoretical 
Biology and Biomathematics; Histocompatibility; Bacterial Genetics; 
Microbial Toxins; Immunochemistry and Immunology; Steroid Recep- 
tors; Cell Culture Techniques; Interferon Standards; Alternatives to 
Insecticide Control; Cell Hybridization; B Lymphocytes in the Immune 
Response. 



Scientific Memoranda 

New data are relatively useless until communicated to those who 
can use them. For the efficient expenditure of research time and 
money, there should be prompt and extensive communications between 
research scientists of this and other countries. 

Close scrutiny of research endeavor reveals that the most valuable 
communications are those conducted informally between scientists. 
Information passed during experiments can help avoid costly errors. 
Discussion of results at the end of an experiment can pass the bene- 
ficial results many months before that same information becomes avail- 
able through publication of a formal manuscript in scientific journals. 
Furthermore, informal communications reveal negative results when they 
occur, and such results often do not appear in the scientific literature. 

With these values in mind, the Scientific Memoranda were started 
as a means for fast, frequent, and informal communications between 
research investigators. Conducted on a worldwide basis, with participa- 
tion by scientists anywhere, the Scientific Memoranda enable a rapid 
flow of informal communications by all researchers in the world inter- 
ested in the subject of a specific Scientific Memoranda. Current projects, 
listed below, are sponsored by the National Institute of Allergy and 
Infectious Diseases (NIAID), the National Cancer Institute (NCI), the 
Blood Bank of the Clinical Center, and the Fogarty International Center. 



1. Interferon Scientific Mennoranda (ISM) 

2. Hepatitis Scientific Memoranda (HSM) 

3. Leprosy Scientific Memoranda (LSM) 

4. Liver Cancer Scientific Memoranda (LCSM) 

About 1,500 active investigators located in 48 countries are 
participating in the Scientific Memoranda. 



Research Coordination Projects 

The Fogarty International Center coordinates certain projects in 
which several Institutes have an interest or mission. With its background 
in international collaboration, FIC also assists the Institutes in initiating 
and managing special intercountry projects. Some examples are: 

1. Lassa Fever. Little is known about this serious viral 
disease, with a very high case-fatality rate, except that it 
occurs in certain parts of Africa, that it is apparently highly 
contagious, and that there is no known specific preventive 
measure or treatment other than hyperimmune serum. On 
the other hand, it resembles Argentine Hemorrhagic Fever 
and Bolivian Hemorrhagic Fever. Taking cues from those 
diseases, a group of scientists concluded that studies should 
be made of the wild rodents in the area of human Lassa 
Fever cases. This resulted in a project involving the Center 
for Disease Control (CDC), NIAID, the Smithsonian Insti- 
tution, a wildlife studies unit of the University of Colorado, 
and the proper authorities of Sierra Leone. The project is 
funded through a contract managed by FIC. 

2. Study of the Influence of Animal Disease Control on 
the Quality of Human Health. The theory, often debated, 
is that efforts to improve disease prevention and control 
in animals, especially food animals, can have a greater 
impact on human nutrition and health, employment and 
standard of living and the economy of a developing coun- 
try, than any other large undertaking. A 2-year study by Dr. 
Wilford S. Bailey of Auburn University was reviewed and 
approved by the Rockefeller Foundation, U.S. Department 
of Agriculture (USDA), CDC, NIAID, and FIC, and is being 
funded, in part, by a contract managed by FIC. A segment 
of the report was presented as a presidential address at the 
American Society of Tropical Medicine and Hygiene. 

3. Expert Evaluations of Influenza Strains and Outbreaks. 
Influenza is a health problem of major concern to all coun- 
tries. Because of the genetic shifts in influenza strains and 



the possibility that new human strains may arise as recom- 
binants of animal or bird strains of influenza viruses, there 
is a worldwide research effort in this field. International 
seminars are being held to assess the evolving knowledge 
from influenza studies, to assure the use of the most up-to- 
date vaccines, and to plan the most productive research 
studies. The results will be evaluated at an international 
workshop and conference. 

The 1978 Influenza Evaluation Project was a joint 
effort of WHO and FIC. In the planning and conduct of 
this project, scientific advice and sponsorship was provided 
by CDC, FDA, NIAID, and USDA. Two invited virologists 
from the People's Republic of China attended. 

4. Study of G6PD Deficiency in Volunteer Subjects. This 
enzyme deficiency is a genetic disorder expressed as hemo- 
lytic anemia on exposure to oxidant drugs or during infec- 
tions. Studies have revealed that anti-oxidant drug 
compounds, including vitamin E, may serve to protect the 
cells against the oxidant damage. 

NIH investigators, Indiana University Hospitals, and 
Johns Hopkins University Medical School made tentative 
arrangements with colleagues in Greece to participate in a 
large-scale clinical trial with patients with this deficiency. 
The FIC arranged for review and funding of this project in 
collaboration with the National Institute of Child Health 
and Human Development (NICHD) and the NIH Clinical 
Center. 

5. Tasl< Force on Use and Needs for Chimpanzees. The 
Endangered Species Act and other forces are cutting off the 
supply of imported chimpanzees needed for a variety of 
research studies. An obvious answer is the development of 
U.S. -based breeding colonies and other resources. The NIH 
Interagency Primate Steering Committee asked FIC for 
assistance in approaching this problem. With FIC guidance 
and management, a task force, including a planning group 
and appropriate specialists, was selected to prepare a report 
within 3 months. The report would include the type of 
studies, the number of chimpanzees needed, and the type 
of available resources. The project is jointly sponsored by 
seven NIH components, CDC, National Science Foundation 
(NSF), and Walter Reed Army Institute of Research 
(WRAIR). 

6. Risl< Assessment of Recombinant DNA Experimentation 
witti E. coli K12. In the period of worry and concern about 
the potential hazards and need for control of DNA recom- 
binant research, there was a great desire for a means to 



assess the risks. Two NIAID intramural scientists, 
Dr. Malcolm F. Martin and Dr. Wallace P. Rowe, offered to 
do the definitive experiments which, if properly designed, 
would prove the current laboratory models and techniques 
to be dangerous or otherwise. Drs. Martin and Rowe applied 
to FIC, and after official review and approval by NIAID and 
FIC, a task force was launched. After a series of planning 
meetings with different groups of specialists, an evaluation 
and consensus development exercise on the subject emerged. 
That session, known as the Falmouth Workshop, laid to rest 
many of the worries about DNA research hazards. The 
report was published as a special supplement to the May 
1978 issue of Journal of Infectious Diseases. 

7. Visit by a Tropical Medicine Group to the People's 
Republic of China. Stemming from negotiations conducted 
by the American Society of Tropical Medicine and Hygiene, 
tentative plans were made for a visit to institutions in the 
PRC by a U.S. scientific group. FIC developed the support 
mechanism and management of the project which enabled 
21 American scientists to make a very useful visit to the 
PRC. NIAID, FDA, and CDC helped in the selection of 
participants. 

8. New Tissue Typing Reagents. In the process of tissue 
typing, originally developed to match compatible organs for 
transplantation, it was discovered that there is individual and 
specific group differences in susceptibility and resistance to 
diseases and disease conditions. A tissue difference in the 
erythrocytes of certain black populations explained their 
"natural" resistance to malaria. 

Tissue typing experts discover, over a period of time, a 
number of new tissue specificities that have not been charac- 
terized, identified and labeled. When sufficient new un- 
knowns are available, a project is developed to have the new 
candidates cross-tested against known standards by about 
100 testing laboratories over a period of several months. The 
accumulated testing data from thousands of tests are 
analyzed by computer and new reagents identified. 

With sponsorship from all NIH components and FDA, 
Interested in tissue typing, the FIC developed and managed a 
supportive contract for the new reagent characterization 
studies. 



Geographic and Policy Studies 

During the 10 years of its existence, the Center has initiated and 
supported a number of studies by U.S. and foreign experts on topics of 



current concern and interest to the health and scientific communities. 
These generally result in monographs published by the Center, or in 
some instances through other publishers, such as scientific journals. 
Many of the studies have been of a geographic nature, concerned with 
various aspects of health services and research in certain other coun- 
tries. Others have been analyses of health policies as viewed from inter- 
national perspectives. 

The nature of these studies is constantly evolving in accordance 
with emerging needs and interests. Indeed, the Center attempts to antici- 
pate that which will be of significance, such as were its earlier studies on 
aspects of Soviet and Chinese biomedical practice and organizations. 

During FY 1978, the following studies were in various stages of 
development: 

Released for publication in FY 1978 — 

• Public Accountability and Peer Review in the United 
States and the United Kingdom by S. Palmer and D.G. 
Gill of the University of Missouri at Columbia. 

© Policies for the Containment of Health Care Costs and 
Expenditures, proceedings of an international confer- 
ence, edited by S. Schweitzer, Georgetown University. 

• Changing National-Subnational Relations in Health: 
Opportunities and Constraints, proceedings of an 
international conference, edited by C. Altenstetter, 
City University of New York. 

• Doctor-Patient Relationship in the Changing Health 
Scene, proceedings of an international conference, 
edited by E. Gallagher, University of Kentucky. 

In preparation — 

• An Introduction to American Medicine, translation 
of an earlier publication into Russian, Spanish, and 
French, by J. Bowers, Josiah Macy, Jr., Foundation. 

e The British National Health Service: A Sociologist's 
Perspective by D.G. Gill, University of Missouri at 
Columbia. 

® Universal Free Health Care in Canada, 1947-1977 by 
G. Hatcher, Albany Medical College of Union 
University. 

• Biomedical Research in Latin America and the Carib- 
bean Area edited by C. Kidd, George Washington 
University. 



10 



Fogarty Scholars-in-Residence Program 

The Fogarty Scholars-in-Residence Program was established in 
1968. Since then, 67 scholars from 18 countries have participated in 
the Program. Participation in the Scholars-in-Residence Program is by 
invitation. Scholars may be nominated from any discipline or field of 
work related to research in the health sciences. Final selection of candi- 
dates is made by the Director of the Fogarty International Center on 
the advice of the Scholars Advisory Panel. Citizens of any country can 
be appointed. 

The Program objective is to conduct research studies on topics 
of contemporary importance in biomedical research. The role of the 
Scholars Program is to permit the inductive exploration of advanced 
research topics in an atmosphere removed from operational laboratory 
or administrative distractions. Scholars are chosen for the excellence of 
their scholarship, their professional standing, and their ability to interact 
with and stimulate others. Some Scholars who fill these criteria are 
invited to work on particular themes under study by the Fogarty Inter- 
national Center itself. Examples of themes are metastasis as a biological 
process, the origin and evolution of molecules, the influence of the 
genetic code on the evolutionary process, the role of nutrition in resist- 
ance to disease, and the relationship between human genetics and 
nutrition. 

In FY 1978, 15 Scholars participated in the Program. Of these, 
eight were biochemists, which consistently claims the largest group of 
Scholars. Their activities ranged from close collaboration in experimental 
projects with intramural scientists to the organization of large confer- 
ences. The Program also furnished an opportunity for a number of 
talented scientists to complete writing for which they otherwise would 
not have had time or support. The freedom from teaching and adminis- 
trative responsibility, coupled with easy access to the library facilities 
of the National Library of Medicine and in the Washington area gener- 
ally, facilitated their task. 

1. Individual Activities and Publications. The publications 
that appeared in FY 1978 are listed in the NIH Annual 
Bibliography. Publications generated by former Scholars are 
also included. 

2. Seminars and Lectures. All the Scholars gave at least 
one lecture or seminar on a subject of their own choosing. 
They also took part in the ongoing seminars and journals 
clubs in different laboratories at NIH. The following is a 
partial list of formal lectures, cosponsored with the Founda- 
tion for Advanced Education in the Sciences: 

December 1, 1977 Michael Schramm "Coupling of Hormone 

Receptors to Adenylate 
Cyclase" 



11 



December 15, 1977 
January 23, 1978 

January 25, 1978 

• February 16, 1978 
February 24, 1978 
April 19, 1978 

April 24, 1978 



H.Schachman 



Nathan Sharon 



M. Rocha e Silva 



G.N. Ramachandran 



Nathan Sharon 



J. Waldenstrom 



Roger Stainer 



"Molecular Sociology 
of a Regulatory Enzyme' 

"Lectins, Their Chem- 
istry and Interaction 
with Animal Cells" 

"Histamine, Anti- 
Histamine and Hista- 
mine Receptors" 

"A Physicist Looks at 
Biology" 

"Lectins in Host Para- 
site Relationship" 

"Mono-Clonal Immuno- 
globulins with Defined 
Activity as Products of 
Random Repression" 

"The Cyano-Bacteria 
Between Two Worlds" 



Dr. Howard Schachman from the University of California came in 
September 1977 and spent two periods of 5 months broken by a visit of 
2 months to several European laboratories. During his sojourn he organ- 
ized several evening discussions on ligand binding and cell surfaces in 
collaboration with the other Scholars. He gave numerous seminars to 
different groups on the NIH campus as well as the public lecture listed 
above. Dr. Jan Waldenstrom worked extensively with NCI staff mem- 
bers on multiple myeloma. Together with Dr. Michael Potter of NCI, he 
convened a working group that examined the fuhdamental scientific 
knowledge about the disease and the clinical aspects of therapy. Primed 
by a Scholar and one or more collaborators on the campus, this type 
of informal workshop is particularly useful for the younger investigators 
as well as for NIH staff. Contact with versatile and erudite individuals 
who are at the top of their profession is always stimulating and leads to 
new insights and perceptions about one's own work. 

Ten evening discussions on subjects related to structure and func- 
tion of membranes were held in the Stone House. The Scholars as a 
group acted as a program committee for these meetings, but the prin- 
cipal impetus came from Drs. G. Salvatore and S. Ratner. They con- 
tacted the speakers, organized the program, invited the extramural 
participants from the Baltimore-Washington area and acted as hosts. 
The meetings were open to the scientific public. These discussions are 
being continued in FY 1979. 



12 



International Research Fellowship and Exchange Programs 

The Fogarty International Center has always viewed as one of its 
most important functions for the advancement of biomedical knowledge 
the sponsorship of opportunities for U.S. scientists to work abroad, and 
foreign scientists to work in the United States for limited periods of 
time in direct collaborative projects. Such experiences broaden horizons, 
stimulate innovation, permit cost-effective sharing of resources, and 
upgrade scientific skills. Through cooperative arrangements with other 
countries and international organizations, the Center administers fellow- 
ship and exchange programs involving both U.S. and foreign scientists. 



International Research Fellowship Program 

The International Research Fellowship Program promotes col- 
laborative biomedical research between U.S. and foreign scientists. The 
Program also offers a training opportunity for promising young foreign 
scientists in the formative stages of their careers. Collaboration provides 
the benefits of combined intensive research approaches, application of 
new and special skills, and the experiences gained from working with 
scientists in a unique environment and research settings outside the 
United States. 

Fellows conduct collaborative research with senior biomedical 
research scientists in medical research institutions in any part of the 
United States as well as in the various intramural research components 
of the NIH. This Program, in addition to enhancing the health objec- 
tives of the U.S. Government, also enhances mutually profitable com- 
munication among scientists and assists in the health manpower develop- 
ment objectives of participating foreign countries. 

In each participating country there is a national nominating com- 
mittee, operating usually under the aegis of the appropriate central 
agency which conducts and supports biomedical research. The country 
committee screens all applicants from that country and nominates 
specified numbers of candidates to the Fogarty Center. These nominees 
compete with nominees from all other countries. Their proposals are 
reviewed by a scientific panel appointed by the Fogarty International 
Center to determine the scientific merit of the proposals. The appli- 
cants are ranked by the panel and awards are made on the basis of 
these rankings. In FY 1978, 86 new and 36 continuation awards were 
made with a total funding of $2,038,000. Numerous publications have 
resulted from the work of the approximately 1,700 Fellows since the 
Program was established in 1958. Collaborative relationships usually 
continue thereafter. Many former Fellows now hold important and 
responsible positions in their home countries. 

As examples of accomplishments, a recent Fellow characterized 
the reaction sequences of the biosynthesis of the antibiotic chlorothricin. 
By selective feeding of the microorganisms that naturally synthe- 



13 



size this antibiotic, he laid the groundwork for the test-tube synthesis 
and commercial production of chlorothricin. Another Fellow studied 
the immunology and physiology of oligodendrocytes. A knowledge of 
these supportive, nonneural brain cells is important for understanding 
the normal functioning of the brain and also certain diseased states such 
as Tay-Sachs disease. Research completed by other Fellows includes 
studies on cardiac microcirculation; immunology of cancer processes; 
toxic and carcinogenic metals in the human environment; dynamics of 
wound healing; hypertensive renal failure and body-fluid balance; im- 
munological reactions of venereal herpes simplex virus; and neuro- 
chemical factors controlling respiration. 



Senior International Fellowship Program 

The Senior International Fellowship Program was initiated in 
1975 to support highly qualified senior and mid-career faculty of U.S. 
schools of medicine, osteopathy, dentistry and public health for periods 
of study and research abroad. In FY 1978, eligibility for these fellow- 
ships was extended to equivalent faculty and staff of other biomedical 
research and educational departments and institutions. Fellowships are 
for 3 to 12 months and require nomination by the applicant's parent 
institution and invitation by a foreign host institution. The purpose of 
such fellowships encompasses not only the benefits of a period of pro- 
ductive scholarship abroad, but also enrichment of research and teaching 
careers and enhancement of scientific cooperation between U.S. and 
foreign institutions. 

Interest and receptivity by U.S. scientists and their institutions and 
foreign host institutions in the Program has continued to grow since its 
initiation. Its productivity is being demonstrated in an increasing body 
of publications resulting from the work abroad. In the period FY 1975 
through FY 1978, a total of 184 awards has been made to scientists 
from 67 institutions in 39 states. They have worked abroad in 25 coun- 
tries, predominantly in Western Europe and the United Kingdom. Of 
this total, 64 awards were made in FY 1978 with funding of $1,023,469. 

Plans are being developed to include an allocation of additional 
Senior International Fellowships in certain special fields as a result of 
recommendations of several national commissions and interests of 
Institutes of NIH. Fields selected are aging, arthritis, diabetes, epilepsy, 
and tropical diseases. It is anticipated that about five fellowships in each 
field will be awarded in FY 1979. Recipients will be selected through a 
separate review and award cycle, with funding derived from the cooper- 
ating lead Institutes: NIA, NIAMDD, NINCDS, and NIAID. Further 
Program interests in the future will be to encourage a greater geographic 
dispersion of foreign host institutions and countries, particularly the 
less-developed or developing, where unique opportunities for research 
and mutual benefit can be expected. 



14 



International Neurosclences Fellowship Program 

In cooperation with the National Institute of Neurological and 
Communicative Disorders and Stroke (NINCDS) and the World Health 
Organization, the International Neurosclences Fellowship Program was 
established in 1977. It is designed to enhance the skills of health pro- 
fessionals and scientists of other countries in the neurosclences through 
training and experience in laboratories and institutions in the United 
States. Fellowships are awarded for periods of 6 to 12 months, and 
continuations beyond a year considered when adequately justified and 
if funds are available. The Program is administered by the Fogarty Inter- 
national Center with funds provided by NINCDS. Applications and 
initial screening are made from countries through WHO and its regional 
offices, with final selection by a committee at NIH on an individual, 
competitive merit basis. Initially, emphasis is placed on the convulsive 
disorders (epilepsy) and the cerebrovascular disorders (stroke). It is 
anticipated that six to eight fellowships can be awarded each year when 
the Program is fully operational. During FY 1978 the Program was being 
announced through WHO and several applications were being processed. 
The first awards are expected to be made early in FY 1979. 



International Tropical Diseases Research Fellowship Program 

The Fogarty International Center, in cooperation with the NIAID 
and with the UNDPA/Vorld Bank/WHO Special Program for Research and 
Training in Tropical Diseases, has established a program for a limited 
number of postdoctoral fellowships for advanced training designed par- 
ticularly for candidates from countries in which specific diseases are 
indigenous. These diseases are malaria, schistosomiasis, filariasis, trypano- 
somiasis, leishmaniasis, and leprosy. Administrative details have been 
developed among the cooperating institutions and announcements have 
been circulated to regional WHO offices and Ministries of Health. The 
first applications are expected during July 1979. 



Other Research Fellowship Activities 

The Swedish Medical Research Council and the Swiss National 
Science Foundation offer postdoctoral research fellowships for U.S. 
biomedical scientists who wish to pursue collaborative research in their 
countries. The Fogarty International Center provides application process- 
ing services and selection recommendations for these programs. The first 
awards by the Swedish program were made in 1963, and to date a total 
of 42 fellowships have been awarded. The Swiss program, begun in 
1973, has awarded a total of 24 fellowships. Of these, three fellowships 
from the Swedish and five fellowships from the Swiss were awarded during 
FY 1978. 



15 



Individual Specialist Health Exchange Programs 

Since 1975, the Fogarty International Center has administered the 
U.S.-U.S.S.R. Individual Specialist Health Exchange Program and the 
U.S. -Romania Health Exchange Program under intergovernmental agree- 
ments in science and technology. These programs provide mutual oppor- 
tunities for health professionals to become personally familiar with 
various aspects of public health and biomedical research activities of the 
participating host country. By providing support for short- and long- 
term exchanges, the programs encourage and facilitate direct collabor- 
ation and communication between the health and biomedical commun- 
ities of the United States and the Soviet Union and the United States 
and Romania. Through the promotion of person-to-person relationships, 
the basic goal of the exchange programs is to expand and disseminate 
scientific knowledge and to foster scientific growth. 

In this endeavor, during FY 1978, the Fogarty International 
Center sponsored 1 1 individuals, one team of 2 persons, and one dele- 
gation of 5 persons, a total of 18 persons, for visits to the U.S.S.R. Two 
individuals and one delegation of three persons were sent to Romania. 
In the same period, 3 individuals, 4 teams, and 2 delegations, totaling 18 
persons, were sent from the Soviet Union to the United States. No 
Romanian specialists participated in the exchange during FY 1978. 

The following American specialists visited the Soviet Union during 
FY 1978: 

Individuals 

• Hugh Johnson, M.D., Rockford, Illinois, Plastic Surgery in 
the U.S.S.R. 

® Elmer Ballantine, M.D., National Eye Institute, NIH: Retinal 
Dystrophy 

• Albert Wertheimer, Ph.D., College of Pharmacy, University 
of Minnesota: Drug Delivery Systems and Pharmacy Services 
in Eastern Europe 

• Lester Breslow, M.D., M.P.H., School of Public Health, 
UCLA: Health Measurement in the U.S.S.R. 

• Leon Roizin, M.D., College of Physicians and Surgeons, 
Columbia University: Biological Psychiatry 

• Samuel Corson, Ph.D., College of Medicine, Ohio State 
University : Psychiatry-Psychobiology 

• Marshall F. Gilula, M.D., Life Energies Research Institute, 
Coconut Grove, Florida: Biofeedback Research 

• David Hawkins, M.D., University of Virginia School of 
Medicine: Psychiatry Education in Eastern Europe 

• Sait Tarhan, M.D., Mayo Clinic, Rochester, Minnesota: 
Cardiac Anesthesiology 

• Joyce Kaufman, Ph.D., The Johns Hopkins University School 
of Medicine: Quantum Chemistry and Pharmacology 



16 



• John Petricciani, M.D., Bureau of Biologies, Food and Drug 
Administration: Virology 

Teams 

• Robert S. Hillman, M.D., Health Sciences Learning Resources 
Center, University of Washington, and Sheilah Hillman, 
Seattle, Washington: Emergency Medical Care for Tourists 
in Russia 

Delegations 

• F.K. Mostofi, M.D., Armed Forces Institute of Pathology; 
Donald E. Henson, M.D., National Cancer Institute; Marjorie 
J. Williams, M.D., Veterans Administration; Robert Stowell, 
M.D., School of Medicine, University of California at Davis; 
and William Hartmann, M.D., Vanderbilt University School 
of Medicine: Pathology in the Soviet Union 

The following American specialists visited Romania during FY 1978: 

Individuals 

• Albert I. Wertheimer, Ph.D., College of Pharmacy, Uni- 
versity of Minnesota: Drug Delivery Systems and Pharmacy 
Services in Eastern Europe 

• David Hawkins, M.D., University of Virginia School of 
Medicine: Psychiatry Education in Eastern Europe 

Delegations 

• J.E. Rail, Ph.D., National Institute of Arthritis, Metabolism, 
and Digestive Diseases; Hilton B. Levy, National Institute of 
Allergy and Infectious Diseases; and Ihor J. Masnyk, Ph.D., 
National Cancer Institute: U.S. -Romania Workshop on 
Biomedical Research Priorities 

The following Soviet specialists visited the United States during FY 1978: 

Individuals 

• Dr. Mikhail Korolev, Institute of Poliomyelitis and Viral 
Encephalitis, Moscow: Virology 

• Dr. Anatoli Erokhin, Second Moscow Medical Institute: 
Urology 

• Dr. Alexandra Demidova, Central Institute of Postgraduate 
Medical Training, Moscow: Hematology 



17 



Teams 

• Dr. Elena S. Ketiladza and Dr. Vera M. Stakhanova, Ivanov- 
sky Institute of Virology, Moscow: Hepatitis Research 

• Dr. Lev I. Malyshev and Dr. Vladimir P. Sergiev, U.S.S.R. 
Ministry of Health, Moscow: Histoplasmosis 

• Dr. Victor A. Knizhnikov and Dr. Boris K. Borisov, Institute 
of Biophysics, Moscow: Radiation Physics 

• Dr. Nadezhda N. Bogomolova and Dr. Yuri S. Borishkin, 
Scientific Research Institute of Viral Preparations, Moscow: 
Rabies Research 

Delegations 

• Professor Tatiana V. Chervakova, Research Institute of 
Obstetrics and Gynecology, Moscow; Dr. Vera I. Lebedeva, 
U.S.S.R. Ministry of Health; Professor Vatsis M. Sadauskas, 
Kaunasskiy Medical Institute, Lithuania; and Dr. Yakov 
Solsky, Ukrainian Ministry of Health, Kiev: Obstetrics and 
Gynecology 

• Dr. Gennadi M. Pakhomov and Dr. Oleg Glazov, Central 
Research Institute of Stomatoloty, Moscow and Dr. Kapiton 
Lakin, Moscow Medical Stomatological Institute: Dental 
Research. 

The establishment of a scientist exchange program was agreed to 
during the year between NIH and the French National Center for 
Scientific Research (CNRS). The program would, in its initial phase, 
support each year up to five French scientists for research in the United 
States and a similar number of U.S. scientists in France. Implementation 
of the program is expected in FY 1979. 



Coordination and Services for NIH International Relationships 

The Fogarty International Center serves as the focal point for the 
coordination of international activities for the Director of NIH. The 
Center, as liaison point, has responsibility for facilitating communica- 
tions between NIH and certain other international offices or agencies, 
including the HEW Office of International Health, the Department of 
State, U.S. embassies abroad, foreign embassies in Washington, D.C., 
and such intergovernmental organizations as the World Health Organiza- 
tion and the Pan American Health Organization. In addition, the Center 
provides certain central services necessary for effective overall NIH 
international affairs. These activities and services supporting the interna- 
tional interests of NIH as a whole for FY 1978 are summarized in the 
following sections. 



18 



Bilateral Agreements for Cooperation in Biomedical Research 

Formal agreements for cooperation between governments of the 
United States and other countries provide the framework within which 
many international activities of NIH take place. While intensive bio- 
medical cooperation may, and does, take place with many countries 
without the need for formal mechanisms, agreements form a basis for 
cooperation in particular situations and circumstances, such as to high- 
light priorities for concentration of mutual effort, to utilize special 
resources, or to overcome constraints of differing social and political 
systems. 

Formal agreements between governments may also take a variety 
of forms, from those of broad scope for educational, cultural, and 
scientific exchange to more specific ones in science and technology or 
the health fields. In some instances health agreements may be subsidiary 
to a broader agreement in science and technology. Less formal technical- 
level agreements may also exist directly between counterpart institutes 
for a particular purpose. 

NIH participation under agreements will usually be together with 
other agencies through channels of HEW. For several agreements, the 
National Science Foundation serves as the executive agency on behalf of 
the U.S. Government. General oversight for formal agreements rests with 
the Department of State. 

The Fogarty International Center serves to coordinate NIH par- 
ticipation in formal agreements and provides operational liaison with 
other levels of HEW, the Department of State, the National Science 
Foundation, foreign embassies, and other appropriate organizations. 
Countries with which there are principal currently active agreements 
involving significant NIH participation include Egypt, France, India, 
Israel, Italy, Japan, Poland, Romania, Spain, Federal Republic of Ger- 
many, the Soviet Union, and Yugoslavia. NIH components have specific 
executive agency responsibilities with respect to the following formal 
agreements: 

Japan: U.S. -Japan Cooperative Medical Science Program 

(NIAID) 
U.S. -Japan Cooperative Cancer Agreement (NCI) 
U.S.-Japan Vision Research Agreement (NEI) 

Romania: U.S. -Romania Individual Health Scientist Exchange 
Program (FIC) 

U.S.S.R.: U.S.-U.S.S.R. Individual Health Scientist Exchange 
Program (FIC) 
U.S.-U.S.S.R. Agreement for Cooperation in Artificial 
Heart Research (NHLBI) 

Programs and activities during FY 1978 under these and other broader 
agreements are reported in detail in the sections of this report of each 



19 



responsible NIH component. Reference should also be made to the 
report of the Special Foreign Currency Program of the Fogarty Inter- 
national Center, which coordinates research projects under agreements 
for utilization of "P.L.-480" and related funds. 



Special Foreign Currency Program 

The objective of the NIH Special Foreign Currency Program (SFCP) 
is to extend NIH research activities into the international biomedical and 
health sciences community by supporting projects in certain countries 
where there are excess U.S. foreign currency credits and resources. 
These projects contribute to the domestic missions of the individual NIH 
operating units in the areas of biomedical research, translation, docu- 
mentation, and dissemination of biomedical and health sciences informa- 
tion. Collaborative research agreements for these individual research 
projects involve U.S. biomedical scientists from within NIH intramural 
laboratories as well as in U.S. academic and foreign research institutions, 
thus assuring that academic, intellectual, and scientific benefits accrue to 
the United States as well as to the participating foreign country, institu- 
tions, and scientists. The program is an integral and significant part of 
the NIH international and domestic effort to advance biomedical science 
knowledge. 

The Special Foreign Currency Program is supported with a unique 
source of funds referred to as "excess currencies." These funds have 
accrued to the credit of the U.S. Government primarily from the sale of 
agricultural products for payments in local foreign (nonconvertible) 
currency under Public Law 480, The Agricultural Trade Development 
and Assistance Act of 1954. It is from this source that the term P.L.-480 
program is derived and is a misnomer when applied to this NIH pro- 
gram. After 1967 such sales had to be made for dollars with the result 
that the U.S. foreign currency balances are not being replenished as they 
are used. Excess currencies are those U.S. -owned foreign currencies in 
a country which are determined by the Office of Management and 
Budget (0MB) to be excess to the needs of the U.S. Government during 
the next 2-year period. Countries where such currencies are available are 
referred to as excess currency countries. When the balance of a currency 
drops below this level, but is of a sufficient amount to be made avail- 
able for special purposes or in limited amounts with restriction, the 
currency is designated by 0MB as a near excess currency. A list of 
countries where currencies are excess or near excess is issued by 0MB at 
the beginning of each fiscal year. The near excess currency countries at 
present are: Morocco, Poland, Tunisia, and Yugoslavia. These currencies 
will continue to decrease in amount and are not available for the NIH 
Special Foreign Currency Program. The excess currency countries are: 
Burma, Egypt, Guinea, India, and Pakistan. 



20 



Funds for the NIH Special Foreign Currency Program are included 
with those of other Public Health Service agencies in the HEW appropri- 
ation for Scientific Activities Overseas, reviewed and acted upon annual- 
ly by the Congress of the United States. Although the appropriation is 
expressed in terms of dollars, it is actually an authorization to use only 
excess foreign currencies up to the dollar equivalent of the amount 
appropriated. This Program does not result in a flow of dollars abroad 
or place an annual requirement upon new tax revenues. 

The appropriation is made to the Office of the Assistant Secretary 
for Health (ASH), HEW. The Office of International Health has responsi- 
bility for formulating policies of the SFCP and apportioning the appro- 
priation. Funds are allotted to NIH on the basis of conformance of a 
project to programs and priorities of HEW and priorities of foreign 
countries that have been negotiated by HEW. When funds are limited 
for some reason, NIH projects must compete with those of other health 
agencies. NIH has responsibility only for reviewing its projects for 
technical merit and contribution to NIH programs. This may occasion- 
ally result in the anomalous situation wherein a project is found meritor- 
ious upon review by NIH consultants but is not selected for funding. 

With the maturation of this and similar programs of other HEW 
and U.S. agencies, the use of these funds has been extended through the 
years from 3 agencies (originally HEW, the Department of Agriculture, 
and the Department of State) to presently 13 science and technology 
agencies. The increased demands upon the funds have depleted balances 
in some cases to where they are marginal, such as in Poland, and to 
where they are no longer available, as in Israel, Tunisia, and Yugoslavia. 
In response to a need for coordination of such increased U.S. activity 
abroad, and to assure effective management and utilization of remain- 
ing funds, the Department of State has entered into bilateral agreements 
with governments of the excess or near excess currency countries for 
cooperation in science and technology, including the health sciences. In 
some cases joint funds, to which each country contributes equally, have 
been established under these agreements to alleviate the impact of the 
loss of total U.S. support and to provide a phase-out period for termin- 
ating projects with maximum data recovery or for seeking support from 
other sources. In India and Yugoslavia biomedical and health sciences 
are provided for under the Science and Technology Board; in Poland 
and Egypt there are separate Biomedical and Health Science Boards. 
Department of State and Office of the Assistant Secretary for Health, 
HEW, representatives serve on these boards, which set the general pro- 
gram parameters and priorities to which NIH programs must conform. 
The success and productivity of such agreements, however, remain 
dependent upon scientist-to-scientist collaboration on problems of 
mutual interest, critically selected for their potential of furthering the 
understanding of normal life processes and disease states of man. This 
characterizes the NIH program and is equally important to the improve- 
ment of health in the countries where the SFCP is active. 



21 



Since the 1962 inception of the NIH-SFCP, 212 U.S. scientists, 
243 foreign scientists, 93 U.S. academic institutions, 110 foreign insti- 
tutions, and 11 NIH Institutes have participated in the program. These 
figures do not include the many foreign professional staff serving in 
supporting but essential roles in the projects. 

More than half of the responsible foreign Principal Investigators 
on the research projects supported under this program have had U.S. 
training. By means of this program, the U.S. -trained foreign scientists 
have been able to maintain an active collaboration with their U.S. 
preceptors and thus remain a part of the U.S. biomedical science com- 
munity. In some instances, by virtue of the research support, these 
young biomedical scientists have been able to introduce modern con- 
cepts of medical training, clinical investigation, biomedical research, and 
patient care that will have long-term effects within the country. The 
immediate contribution to biomedical research from these countries is 
thus only one of the benefits from this program. 

Through the SFCP, NIH has engaged the unusual talents of some 
of the most outstanding scientists throughout the world and utilized 
unusual research opportunities for health-related projects of importance 
to the American people. A number of significant advances in biomedical 
research have been reported and documented in over 3,000 publications 
in the scientific literature as the result of U.S. and foreign investigators 
pooling their talents and resources to search for information which will 
help in the understanding, prevention, and treatment of diseases. 

It is not the intention or objective of NIH to provide technical 
assistance or foreign aid under this program. These are activities outside 
the statutory mission of NIH. However, it must be recognized that 
research projects, if they are to be conducted in a country, must repre- 
sent the mutual interest of the host country, its institutions, and medi- 
cal personnel, and that therefore financial, academic, intellectual, and 
scientific benefits do accrue to the host country. Although this has not 
been a primary consideration of NIH, the HEW and the State Depart- 
ment have recognized that this program has made significant ancillary 
contributions to humanitarian, technical assistance, U.S. policy, and 
political objectives of the United States. The biomedical and health 
■science base established by the NIH-SFCP in past years has served 
as the basis for formal bilateral agreements expanding collaboration of 
other U.S. agencies into the areas of science and technology in Egypt, 
India, Israel, Poland, and Yugoslavia. 



Egypt 

The Special Foreign Currency Program in Egypt is characterized 
by the participatory role of the Fogarty International Center in the 
activities of the Subcommittee for Biomedical Research of the U.S.- 
Egypt Joint Working Group on Health Cooperation established by an 



22 



agreement of October 28, 1975. The Director of the Fogarty Interna- 
tional Center is the U.S. Cochairman and the SFCP Branch serves as 
the Secretariat for the Subcommittee. Four major events marked the 
activities of the SFCP during this year. They were: (1) the first meet- 
ing of the full Subcommittee for Biomedical Research held in Cairo, 
January 1978; (2) the U.S.-Egypt Joint Working Group on Health 
Cooperation meeting in Egypt in June 1978; (3) the survey of Liver 
Disease and Hepatitis; and (4) the projected limitation on funds for 
future years. 

The U.S. component of the Subcommittee for Biomedical Re- 
search selected several U.S. researchers working in areas identified during 
previous meetings of the Joint Working Group on Health Cooperation 
and Subcommittee for Biomedical Research as of importance to Egypt, 
i.e., (1) tropical diseases; (2) infectious diseases and immunology; (3) 
rabies, (4) diabetes; (5) enteric and diarrheal (viral and bacterial) dis- 
eases; (6) nutrition; and (7) child health, and arranged for their par- 
ticipation in a survey of these topics during its January 1978 meeting 
in Egypt. Although liver disease and hepatitis were also identified at 
that time as of importance, consideration was deferred for a subsequent 
visit of a survey team of researchers on these subjects. During the visit, 
working groups composed of U.S. and Egyptian researchers in the fore- 
going priority areas were organized and their deliberations and recom- 
mendations were recorded in individual reports which were incorporated 
into the report of the subcommittee. The conclusions of these working 
groups and the subcommittee were reviewed with the Minister of Health. 
This report will serve as the Biomedical Research Subcommittee's plan 
for developing its research program and integrating its activities with 
those of other subcommittees. 

The subcommittee recommendation with the broadest implication 
for research program development and potential impact on health in 
Egypt was the proposal for the establishment of a center for collection 
of incidence, prevalence, morbidity, and mortality data, as a basis for 
objectively determining the disease and health problem priorities of 
Egypt and evaluation of intervention programs. These centers will also 
serve as sites for the conduct of research, such as a comprehensive study 
of infant enteric and diarrheal diseases identified by the subcommittee 
as its second priority. 



India 



The NIH collaboration with Indian scientists under the Special 
Foreign Currency Program began with the signing of the first research 
agreement in 1961 for a study of protein malnutrition. Despite the 
research potential of India and the close professional and academic 
ties between U.S. and Indian scientists, the program remained at a mod- 
est level of activity until it was interrupted in July 1972 by the Indian 



23 



Government's decision to undertake a review of all U.S. -rupee supported 
programs and to establish new project review and selection procedures. 
The SFCP was essentially phased out over a 5-year period subsequent to 
that date. 

The program has always been well received by individual scientists 
within India and among their U.S. counterparts. However, the lack of 
uniform Government policy in India concerning the SFCP, the large 
number of autonomous Government agencies and semiautonomous 
institutions representing both diverse and complementary interests, and 
the absence of a coordinating point with uniform procedures have been 
a deterrent to expansion of the program to a size commensurate with 
Indian research potential. At one time, the NIH-SFCP included projects 
which originated from and were the responsibility of six different Indian 
Government agencies. 

This situation was changed significantly by the Agreement between 
the Government of the United States of America and the Government 
of the Republic of India to Establish a Joint Commission on Economic, 
Commercial, Scientific, Technological, Educational, and Cultural Cooper- 
ation which was signed on October 28, 1974, by Secretary of State 
Kissinger and Mr. Y.B. Chavan, Minister for External Affairs of the 
Republic of India. The agreement provided for establishing subcommis- 
sions for the fields of economic and commercial development, scientific 
and technological cooperation, and educational and cultural cooperation. 
The Subcommission on Science and Technology was given responsibility 
for health as well as industry and agriculture. The first meeting of the 
U.S.-lndo Subcommission on Science and Technology was held in Janu- 
ary 1975 in Washington, D.C. Subsequent meetings were held in January 
1976 in New Delhi and in June 1977 in Washington. 

At the first meeting of the Subcommission on Health, the Min- 
istry of Health, and Indian Council of Medical Research (ICMR) took 
the initiative, setting priorities for collaboration which they have kept 
sharply in focus during subsequent meetings and in guiding program 
development. The priorities agreed upon at the initial meeting, and 
which remain in effect are: (1) communicable and infectious diseases, 
with particular emphasis on prevention and control techniques for such 
diseases as tuberculosis, leprosy, malaria, filariasis; (2) reproductive 
biology and fertility control; (3) health delivery systems for efficient 
utilization of medical and paramedical manpower; (4) nutritional, 
metabolic, and degenerative diseases; (5) toxicologic research on natu- 
rally occuring toxins in foods, pesticides, and drug residues; and (6) 
other such areas of biomedical and health science research as may be 
proposed and agreed upon as being of mutual interest and importance. 

During this year, definitive action was taken on 15 projects of 
interest to NIH for which an Indian decision had been pending for an 
extended interval during the review period. Although none was selected 
for support by the NIH-SFCP, several of those found meritorious but 
for which collaboration was not essential to conduct of the study, were 
supported with Department of Science and Technology or ICMR funds. 



24 



The collaboration was reestablished under the newly created Sub- 
commission with initiation of two projects which were activated this 
year: one, a study of urolithiasis, especially of the bladder, a significant 
problem in India; and the other a more fundamental investigation of the 
physical-chemical basis for the therapeutic properties of lithium, and of 
the pathology of reactions of free radicals in biological systems. The 
renewal of an unusually productive study of oral cancer and associated 
oral pathology, which was interrupted for 3 years during the review 
period, was also activated. 

The SFCP has worked closely with the ICMR and NIH Institutes 
in directing U.S. attention to such high priority problems in India as 
leprosy. In the previous year a team of four U.S. scientists attended an 
initial session in India of a two-part Leprosy Research Planning Confer- 
ence (March 1976) at the invitation of the ICMR and under the auspices 
of the SFCP. The conference was designed to introduce the U.S. partici- 
pants to Indian leprosy problems, clinical and research facilities, and 
clinical investigators and biomedical scientists. The survey panel visited 
12 institutions in India. In this year (October 1977) the second part of 
the Leprosy Planning Conference was held, in which 10 Americans 
participated. This second session was dedicated to identifying potential 
lines of investigation, arranging scientist-to-scientist collaborations and 
preparing synoptic research protocols to be developed subsequently 
into detailed project descriptions for submission to the ICMR and for- 
warding to NIH. Among the aspects of leprosy given attention at this 
meeting were immunology, immunogenetics, microbiology, pathology, 
cultivation, animal models, nutrition, vaccines, chemotherapy, bio- 
chemical pharmacology of antileprosy drugs, and drug development. 
These activities have been productive of research proposals accepted by 
the ICMR and presented for consideration by NIH. 

The NIH collaborates informally with the Madras Medical College 
and Tuberculosis Chemotherapy Center in a study of the immunological 
and clinical aspects of human filariasis, with particular attention to 
tropical eosinophilia an active and productive area of special interest to 
the ICMR. Malaria and reproductive physiology areas, which NIH has 
surveyed in cooperation with the ICMR, remain of mutual interest and 
offer potential for future cooperation. 



Israel 

In FY 1968, the balance of U.S. -owned Israeli pounds was de- 
pleted to the point where it was determined that funds would no longer 
be available for the SFCP. Thisjwas'disruptive to biomedical and health 
sciences in Israel, where 50 percent of the research effort in these fields 
was dependent upon U.S. support. In anticipation of the loss of these 
funds and to provide some alternative support, the Department of 
State and the Israeli Government signed an agreement on September 



25 



27, 1973, establishing the U.S. -Israeli Binational Science Foundation, to 
which each country contributed equal amounts of Israeli pounds in a 
total equivalent to $60 million. The income from the investment of 
these funds provides for a modest number of new projects annually. 
This was the first of several joint funds to be established subsequently 
under similar circumstances in other countries. 

Applications for support from the Foundation are submitted to 
the Executive Director of the U.S.-lsrael Binational Foundation, P.O.B. 
7677, Jerusalem. The Foundation reviews and evaluates the technical 
merit of applications. The opinions of U.S. scientists are solicited in the 
review process. The Board of Governors of the Foundation, on which 
U.S. Government representatives and private citizens, as well as Israeli 
members serve, makes recommendations on projects to be funded. By 
the terms of the agreement, the Foundation projects must contribute 
to the biomedical science programs in the United States as well as Israel. 
In keeping with this requirement, NIH is requested annually to review 
the newly submitted applications for their relevance to NIH biomedical 
research programs. This function is carried out by the NIH-SFCP. The 
Foundation also sends to NIH annual progress reports from all bio- 
medical science projects. These are also received, and if necessary dis- 
tributed, by the SFCP. Information about the Foundation, its Annual 
Report, and application forms are maintained by the SFCP Branch and 
distributed upon request. The Foundation's most recent (1977) report 
lists 118 active projects in the categories of Life Sciences and Health. 
12 of which are collaborations with NIH intramural staff. 



Pakistan 

There is no Science and Technology or Health Agreement with 
Pakistan. The modest size of the NIH Special Foreign Currency Program 
and the delays to which projects are subject in the review process may 
be attributed to the lack of recognition given to the biomedical and 
health sciences, in contrast to that which a formal bilateral agreement 
accords them in other countries. The Pakistan Medical Research Council 
and Pakistan Science and Technology Council always have been recep- 
tive to collaborative research proposals. The Ministry for Finance and 
Economic Planning, however, requires that research projects be an 
integral part of the Five Year Plan. Predictably, intellectual spontaneity 
does not coincide with economic planning cycles, with the result that 
discouraging delays occur in the process of obtaining authorization for 
use of funds to support individual research projects. The recent focus of 
the program has been upon the chemistry of products of potential 
pharmacological importance from indigenous plants. The Council for 
Scientific and Industrial Research has been active in this area and a 
number of proposals from this organization have been submitted to 
NIH. 



26 



Poland 

A Memorandum of Understanding between the United States and 
Poland, signed on March 14, 1962, designated NIH as the focus for 
development of a collaborative research program in the biomedical 
sciences. The first NIH research collaboration in Poland was a study of 
neuromuscular diseases in the Department of Neurology of the Medical 
Academy of Warsaw, which is still active but in a much different form. 

With expansion of the program and changes in its emphasis, as 
well as reorganizations of HEW, responsibility for the program was 
ultimately transferred to the Office of International Health, Office of 
the Assistant Secretary for Health, and the original bilateral agreement 
which served as the basis for the collaboration was revised to bring it 
up to date and to expand its scope. 

On March 15, 1973, during the visit of the Minister of Health 
of Poland, a revised Memorandum of Understanding was signed by the 
Secretary of HEW and Dr. Marian Sliwinski, the Polish Minister of 
Health. This agreement, for the first time, formally provided for: (1) the 
exchange of scientists; (2) the development of mutually agreed-upon 
priorities; and (3) the annual review and revision of these priorities. 

On October 8, 1974, during the visit of Mr. Edward Gierek, First 
Secretary of the Polish United Workers Party, the health agreement of 
1973 was revised and elevated to the status of a country-to-country 
agreement. This agreement included Iwo new provisions: (1) establish- 
ment of a U.S. -Polish Joint Committee for Health Cooperation; and 
(2) funding of HEW projects from the Marie Sklodowska-Curie Fund. 
This Joint Fund was established by the separate agreement for Funding 
of Cooperation in Science and Technology, which was also signed at 
that time (October 8, 1974). This document, which also provided for 
the establishment of a U.S. -Polish Joint Board (for science and tech- 
nology), was an implementation of the Science and Technology Cooper- 
ation Agreement, signed in October 1972 during the visit of the Presi- 
dent of the United States to Poland. 

About the time that the Joint Fund was created, the Office of 
Management and Budget placed a limitation on use of funds, and the 
Treasury Department and the Department of State issued a schedule for 
phasing out full or total support of projects with U.S. -owned ziotys by 
December 31, 1976, at which time Poland was removed from the excess 
currency list. 

With the establishment of the Joint Board and the Joint Fund, 
and the announcement of the U.S. funding phase-out schedule, the 
Polish Government agreed to make contributions to the Joint Fund in 
amounts equal to those which HEW and other agencies deposited each 
year during the 4-year phase-out period to December 31, 1976, for 
support of NIH and other agency research projects. The Polish contri- 
butions to the Joint Fund were to become available January 1, 1977. 
Unfortunately, the time and difficulty of working out fiscal and admin- 
istrative procedures for the comingling and disbursement of U.S. and 



27 



Polish contributions to the Joint Fund, subject to fiscal constraints of 
the two Governments, was greater than anticipated. These procedures 
were finally agreed upon at a meeting of the U.S.-Polish Joint Board 
for Science and Technology, April 1978, in Washington. 

The current program priorities were established at the first meet- 
ing of the U.S.-Polish Joint Committee for Health Cooperation and 
reviewed at the second meeting with the result that oncology, which had 
been deleted at the time of the first annual review, was reinstated. The 
last formal meeting of the Committee was in March 1976 and the priori- 
ties, which have been reported previously, were not reviewed at that 
time. The Committee coordinators, however, have met annually since 
that date to transact business when necessary. 

The hiatus of support in excess of 2 years and resulting uncer- 
tainty as to when and under what conditions funds would be available 
disrupted the SFCP continuity and discouraged many U.S. scientists 
interested in collaborating with associates in Poland. The agreement 
upon Joint Fund procedures permitted NIH to immediately renew 
support of projects which had been interrupted during this period 
and to activate the first new project to be supported under these pro- 
cedures. Each project supported by the Joint Fund has travel funds 
for visits of collaborating scientists. However, the Joint Fund has no 
travel funds available for planning purposes. This is a major deterrent to 
establishing collaborations between scientists who need to meet for the 
purpose of learning about the environment in which the project will be 
conducted, assessing joint resources, and developing the experimental 
design of the study in sufficient detail that it can successfully withstand 
the scrutiny of the NIH review process. With evidence that the Joint 
Fund is operational, the SFCP has begun to resume a normal level of 
operation. This perception was further reinforced by the subsequent 
visit of the Director of the Fogarty International Center to the Coordin- 
ating Commission for the Polish-American Scientific Collaborations, the 
Scientific Council to the Ministry of Health and Social Welfare, and to 
several NIH research projects and other research centers in Poland. 



Yugoslavia 

The NIH-Yugoslav research collaboration under the Special For- 
eign Currency Program was initiated in 1962. In March 1972 it was found 
unexpectedly that the balance of U.S.-owned dinars was depleted to 
the point that they were no longer available for this program of NIH 
and other agencies. The Department of State negotiated the Agreement 
between the Government of the United States of America and the Govern- 
ment of the Socialist Federal Republic of Yugoslavia on Scientific and 
Technological Cooperation, which was signed on May 18, 1973. 

This agreement established a Joint Fund for the support of scien- 
tific and technological projects, including health, and a U.S.-Yugoslav 



28 



Joint Board on Scientific and Technological Cooperation to administer 
the Fund iri the amount of $14.4 million (equivalent) from equal dinar 
contributions by each country. At a meeting of the Joint Board, May 
14-18, 1973, it was apparent that the income from this Fund would 
have little effect in moderating the loss of financial support; the decision 
was then made to commit all the funds to provide limited support for 
projects during a phase-out period. NIH was allotted funds for 24 
projects. Of these, eight remain active as a result of reducing expendi- 
ture rates to extend the financial basis for collaboration. 

The U.S.-Yugoslav Joint Board on Scientific and Technological 
Cooperation meets twice a year, a Fall meeting in Yugoslavia and a 
Spring meeting in the United States. The U.S. members of the Board 
are the Science Attache from the American Embassy in Yugoslavia and 
a representative from the staff of the Bureau of Oceans and Interna- 
tional Environmental and Scientific Affairs, U.S. Department of State. 

The Joint Board at its October 1977 meeting in Yugoslavia ap- 
portioned a small amount of dinars from both uncommitted funds 
carried forward from unused initial deposits and from interest accumu- 
lated on deposits among several projects of various U.S. agencies. Two 
NIH projects were the beneficiary of these funds. 

With diminishing funds the Joint Board has been occupied with 
efforts to maintain collaboration between scientific communities of the 
two countries and finding a basis for transition to the other sources of 
support. To this end, a list of proposed research topics in various fields 
of science and technology was presented at this meeting for review by 
U.S. agencies. In a followup of this effort, synoptic proposals outlining 
these topics in greater detail were presented at the May 1978 meeting 
of the Joint Board in Washington for more extensive consideration by 
interested agencies. Forty -one of these were referred to NIH. 

The U.S.-Yugoslav bilateral agreement has a unique provision for 
matching U.S. dollar support of any former NIH-SFCP, Joint Board or 
new research project of mutual interest on an equal-share matching basis 
through the Joint Fund administered by the U.S. -Yugoslavia Joint 
Board on Scientific and Technological Cooperation. Scientists in Yugo- 
slavia are also eligible and encouraged to apply directly to NIH for 
support from the regular (dollar) research grant programs. 



International Visitors Center 

The NIH attracts many scientists, administrators, and health pro- 
fessionals from all parts of the world to visit, examine and exchange 
ideas and techniques in the biomedical sciences. The International 
Visitors Center (IVC) has been established by the Fogarty International 
Center to provide the administrative management of the NIH Visiting 
Program for the Institutes and Divisions of NIH, and to provide a full 
range of advisory and facilitative services to foreign scientists in the 



29 



Guest Scientist Program and the Expert Programs of the BID's. In 
addition, the IVC serves as a focal point for short-term foreign visitors 
to assist in the reception and programming of their visits to NIH. 

In addition to the NIH Visiting Program participants, the Interna- 
tional Visitors Center provided a full range of advisory and facilitative 
services to some 350 other foreign scientists who came to NIH during 
FY 1978 to participate in NIH research studies. Among this number 
were 232 scientists from 37 foreign countries, primarily the affluent 
developed ones, who came as Guest Scientists funded by their coun- 
tries, international agencies, or U.S. sources other than NIH. An increase 
in the number of Guest Scientists from the developed nations has been 
observed, and it is anticipated that this trend will continue in the 
future. 

The additional 120 scientists, whom we have served, include 
experts appointed by the Institutes, and scientists coming to NIH under 
sponsorship of the bilateral agreements in which NIH participates. 
Similar increases in the numbers of experts and exchange scientists are 
expected in the future, due to the expansion of the programs repre- 
sented by this group. 

The International Visitors Center also serves as a focal point for 
foreign scientists, administrators, health professionals, and dignitaries 
from all parts of the world who want to visit NIH during the course of 
their travels. The IVC is responsible for arranging appointments, brief- 
ings, demonstrations, and tours of the biomedical facilities in accordance 
with the special interests of these international visitors. During FY 1978, 
extensive programs were arranged for 78 visitors from 27 countries, and 
there were numerous other visitors for more limited activities. 



The NIH Visiting Program 

This program offers distinguished and talented scientists at all 
levels of their careers the opportunity to come to NIH to share the 
tremendous resources of the NIH for an interchange of scientific infor- 
mation and training. This program enhances the environment of NIH by 
facilitation of the advancement of knowledge in the health sciences, 
and exerting a significant influence on the development of biomedical 
research internationally by implementing close and continuing working 
relationships between Visiting Program participants and the research 
staff of NIH. 

The NIH Visiting Program is composed of: Visiting Fellows, 
authorized by Sections 207(g) and 307 of the Public Health Service Act 
and 42 CFR, Part 61A of the PHS Regulations for regular fellowship 
awards; and Visiting Associates and Visiting Scientists, authorized by 
Sections 207(g) and (h) of the PHS Act, and Part 61 B of the PHS Regu- 
lations for service fellowship appointments. 

The NIH Visiting Program, which was initiated in August 1950, 
has continued to grow at an accelerating rate. In FY 1965, there were 



30 



157 participants at a cost of $1.2 million; in FY 1971, 225 at $2.6 
million; and in FY 1976, 624 at $6.8 million. The following table con- 
trasts the participation in the last 2 years: 



NIH VISITING PROGRAM 



FY 77 



FY 78 



Foreign 


Number of 




Number of 




Country 


Participants 


US$ 


Participants 


US$ 


Argentina 


7 


82,301 


8 


73,639 


Australia 


14 


127,922 


24 


210,527 


Austria 


5 


49,693 


8 


57,444 


Belgium 


17 


172,280 


15 


168,576 


Bolivia 


1 


4,452 


-- 


... 


Brazil 


7 


38,330 


5 


63,051 


Bulgaria 


1 


6,214 


-- 


... 


Cameroon 


2 


25,298 


1 


16,849 


Canada 


17 


171,492 


24 


218,929 


Chile 


3 


24,873 


2 


28,634 


China-Taiwan 


38 


389,062 


12 


156,415 


Czechoslovakia 


1 


19,169 


2 


10,125 


Denmark 


4 


29,695 


1 


6,087 


Egypt 


4 


43,307 


4 


59,104 


Finland 


2 


18,153 


5 


63,696 


France 


10 


68,947 


19 


141,193 


Germany 


12 


116,185 


15 


158,517 


Greece 


6 


64,325 


7 


118,228 


Guatemala 


1 


10,849 


1 


10,763 


Hong Kong 


1 


1,758 


4 


17,540 


Hungary 


4 


34,619 ■ 


3 


15,939 


Iceland 


-- 




1 


9,151 


India 


61 


582,876 


67 


642,713 


Iran 


1 


3,734 


-- 


... 


Ireland 


2 


28,543 


2 


36,863 


Israel 


44 


614,579 


44 


535,598 


Italy 


48 


505,228 


53 


562,730 


Japan 


156 


1,643,427 


175 


1,944,871 


Korea 


1 


3,667 


6 


22,903 


Lebanon 


-- 


... 


3 


21,551 


Luxembourg 


-- 


... 


1 


3,029 


Malaysia 


2 


15,397 


2 


22,259 


Mexico 


5 


43,072 


3 


49,173 


Nepal 


-- 


... 


1 


1,320 


Netherlands 


5 


54,800 


7 


36,465 


New Zealand 


5 


44,737 


1 


6,133 


Nigeria 


1 


13,821 


2 


38,349 


Norway 


3 


38,381 


2 


4,218 


Pakistan 


2 


18,889 


3 


48,048 


Peru 


2 


34,689 


2 


30,805 



31 



FY 77 FY 78 



Foreign 


Number of 




Number of 




Country 


Participants 


US$ 


Participants 


US$ 


Philippines 


2 


34,250 


1 


2,920 


Poland 


14 


152,927 


9 


76,766 


Portugal 


1 


9,236 


1 


1 1 ,840 


South Africa 


5 


59,850 


2 


70,557 


Spain 


9 


97,954 


12 


113,285 


Sri Lanka 


2 


18,115 


3 


26,281 


Sudan 






1 


1,746 


Sweden 


7 


73,228 


14 


176,121 


Switzerland 


13 


168,789 


14 


198,090 


Thailand 






1 


3,157 


Turkey 


2 


17,285 


3 


22,751 


United Kingdom 


65 


668,594 


73 


894,997 


Venezuela 


1 


10,839 




... 


West Indies 


1 


1 1 ,690 


-- 


... 


Yugoslavia 


2 


23,703 




— 


Total participants: 










Foreign countries 


617 


6,266,639 


675 


7,269,174 


United States* 


178 


2,763,559 


187 


2,925,379 


Grand Total 


795 


$9,030,198 


862 


$10,194,553 


Total countries: 


60 




57 





* U.S. includes citizens, permanent residents and conditional immigrants. 

During FY 1978, in the NIH Visiting Progrann, there were 513 
Visiting Fellows, 184 Visiting Associates, and 165 Visiting Scientists. 
During the same year, there were 276 new appointments and 265 term- 
inations, providing the turnover so vital to the exchange nature of the 
program. A significant number of former participants in the program 
returned to NIH in subsequent years, bringing their advanced knowledge 
and new insights to revitalize their working relationships with NIH 
staff scientists. Some of the international collaborative programs had 
their inception in the NIH Visiting Program. In addition, some Fogarty 
Scholars were former participants in the Visiting Program. Among the 
latter are former Visiting Scientists Torsten Teorell of Sweden; Osamu 
Hayaishi of Japan; Michael Sela of Israel; Ruggero Cepellini and Gae- 
tano Salvatore of Italy. 

Four former Visiting Scientists in the Visiting Program were 
awarded the Nobel Prize in Physiology or Medicine: 



32 



1947 — Dr. Bernardo A. Houssay of Argentina, for the discovery 
of the role of pituitary hormone in sugar metabolism. 

1962 — Sir Francis H.C. Crick of the United Kingdom, for the 
discovery of the molecular structure of nucleic acids and 
its significance in the transmission of genetic information. 

1968 — Dr. H. Gobind Khorana of the United States, for transla- 
tion of the genetic code and its function in protein syn- 
thesis. Dr. Khorana shared this award with Dr. Robert W. 
Holley and Dr. Marshall W. Nirenberg, the latter, an NIH 
scientist. 

1976 — Dr. D. Carleton Gajdusek of the United States, for work 
on atypical slow viruses. 

During the many years of his work leading to the Nobel Prize, 
Dr. Gajdusek collaborated with two Australian scientists, who periodical- 
ly returned to his NIH laboratory under Visiting Program sponsorship. 
^^ Dr. Vincent Zigas has come as a Visiting Scientist on a number of occa- 
sions since 1958 to work with Dr. Gajdusek and bring to the studies the 
benefits of his field observations on Kuru in New Guinea. Dr. Michael 
Alpers, also of Australia, has also come to NIH, both as a Visiting 
Associate and a Visiting Scientist, to work with Dr. Gajdusek in this 
study. This is a fine example of the benefit of this program which 
enables a continuing exchange of scientists and the encouragement of 
long-term collaborative studies in the geographical locations where such 
research can prosper most effectively. 

It is anticipated that the growth pattern of the NIH Visiting Pro- 
gram will continue to follow the experience of recent years. 



International Education Program 

The International Education Program, originally established in 
1945, was under other Public Health Service agencies before being 
assigned to the Fogarty International Center. The Program has two 
principal functions: 

1. The location and arrangement of short-time training 
placements for foreign health professionals coming to the 
United States under the sponsorship of the World Health 
Organization, the Agency for International Development, 
private foundations, or as voluntary visitors. Training pro- 
grams vary from technical training for individuals from 
underdeveloped countries to programs for highly specialized 
personnel from advanced countries. 

2. The solicitation and receipt of applications from Amer- 
ican health professionals for WHO fellowships to study 



33 



advanced aspects of health care throughout the world. Geri- 
atrics, neonatal care, and Government-financed health sys- 
tems are the most popular fields of study for Americans. 

During FY 1978, 244 training requests were from WHO, 67 from 
the Agency for International Development, and 9 from voluntary visitors 
through the Department of State. The Center's WHO fellowship selec- 
tion committee reviewed 63 applications, recommending that 20 of 
these be awarded a WHO fellowship. 

During FY 1978, these training programs varied in length from 1 
week to 1 year, with an overall average of 3 months. 



U.S. Government Support of 
The Gorges Memorial Laboratory, Panama 

On May 7, 1928, President Coolidge signed Public Law 30-750 
whereby Congress authorized a permanent annual appropriation to the 
Gorgas Memorial Institute of Tropical and Preventive Medicine, Inc., 
Washington, D.C., for the operation and maintenance of a research 
laboratory in Panama. This action, together with land and building 
donated by the Government of Panama, permitted establishment of the 
Gorgas Memorial Laboratory. This year, 1978, thus marks the 50th 
anniversary of its founding. Since FY 1971, the Fogarty International^ 
Center budget has provided the annual U.S. core support funds. The 
Center maintains general program oversight. 

The Laboratory conducts a diversified program of research in 
tropical disease of importance to the United States, Panama, and the 
region. Particular emphasis is placed upon virology, parasitology, and the 
effects of environmental change on disease vectors and transmission. In 
addition to research, the Laboratory makes its facilities available for 
visiiing scientists and the training of professional personnel. It has coop- 
erative arrangements with several U.S. universities for graduate and 
medical student study and course credit. Formal training courses in 
tropical medicine are conducted several times a year for U.S. Navy 
medical officers. 

The work of the Laboratory is summarized in annual reports to 
the Congress and in publications in the scientific literature by its staff. 
Highlights during FY 1978 included: 

— demonstration that Gamboa virus is transmitted transovari- 
ally in the Aedes squamipennis mosquito. This is the first 
demonstration of transovarial transmission of a neotropical 
virus and raises the question of the importance of this 
mechanism in maintaining arbovirus between outbreaks of 
disease. 



34 



— an advance in the ability to classify insects was made pos- 
sible through the isozyme technique, which permits rapid 
speciation of insects that previously could be differentiated 
only with difficulty. 

— continuation of antimalarial drug evaluation using the Aotus 
monkey gave promise of effective compounds for the future. 
Seroepidemiologic methods indicate the feasibility of rapidly 
determining the malarial status of an area. 

— support to the national authorities of Honduras, Guatemala, 
and El Salvador in the investigation of an outbreak of 
dengue, the first reappearance of the disease in over 30 
years. The rapid spread of dengue is of great concern since it 
indicates the prevalence of Aedes aegypti, which could rein- 
troduce yellow fever into these countries. 

— expansion of the Laboratory's range of research interest 
occurred with the detection of an area of Panama with an 
apparent high prevalence of cancer of the cervix. A study 
was initiated with a view to defining its epidemiology, cause, 
and ultimate prevention. U.S. Government core support of 
$1.4 million was provided in FY 1978. 

In addition, the Laboratory derived $484,454 from research grants and 
contracts from other sources. 



35 



International Cooperation by Components of NIH 



National Cancer Institute 



Introduction 

Striking differences in geographic, environmental, occupational, 
and social conditions of peoples throughout the world suggest that these 
variations must have a critical influence on the incidence and the types 
of cancer prevalent in a given area. Through collaboration with interna- 
tional organizations and scientists from foreign institutions, the National 
Cancer Institute (NCI) is becoming increasingly aware of the crucial 
factors for improving the quantity and quality of health services re- 
quired for coping with the cancer problem. By participation in interna- 
tional cancer research activities, the NCI can ensure more rapid advances 
in basic research and its application to the clinical management and con- 
trol of cancer. 

Accordingly, the contribution of NCI to the international struggle 
against cancer includes (1) continuing support of research on cancer by 
foreign scientists who are highly qualified and have unique expertise; 

(2) support of cooperative research programs, principally under bilateral 
agreements with foreign governments, institutions, or organizations; 

(3) maintenance of liaison and research collaboration with international 
organizations and agencies that have well-defined objectives in cancer 
research and cancer treatment/prevention; (4) support of training foreign 
scientists in the United States as well as the interaction of American 
scientists with colleagues in foreign laboratories; and (5) management 
and operation of an International Cancer Research Data Bank for pro- 
moting and facilitating, on a worldwide basis, the exchange of informa- 
tion for cancer research and treatment. 



The International Cancer Research Data Bank Program 

The International Cancer Research Data Bank (ICRDB) Program 
is one of the National Cancer Institute's principal modes for woi'ldwide 
communication of scientific information. Its objective is to promote and 
facilitate the exchange of information between cancer scientists and to 
disseminate information to physicians through cancer centers and other 
appropriate organizations for the ultimate benefit of the cancer patient. 
Mandated by the National Cancer Act of 1971, this mission of the 
ICRDB program is accomplished by (1) the operation oi several on-line 



36 



computer data bases; (2) the publication of a number of technical 
bulletins; and , (3) the support of a variety of specialized information 
collection, analysis, and dissemination activities. 

The major feature of the ICRDB program is a computer-based 
information system called CANCERLINE (Cancer Information On-Line). 
CANCER LINE links the computer system at the National Library of 
Medicine in Bethesda with terminals in more than 700 locations 
throughout the United States and 11 foreign countries: Australia, Brazil, 
Canada, France, West Germany, Iran, Japan, Mexico, South Africa, 
Sweden, and the United Kingdom. 

CANCERLINE contains three data bases. One, CANCERLIT 
(CANcer LITerature), contains more than 150,000 abstracts of the 
world's published literature in all fields of cancer. Another data base, 
CANCERPROJ (CANCER PROJects), contains more than 20,000 
descriptions of cancer projects currently in progress. Included are more 
than 4,000 descriptions from foreign investigators located in some 60 
different countries. The project descriptions are selected and processed 
by the Current Cancer Research Projects Analysis Center (CCRESPAC), 
which is operated for the ICRDB program by the Smithsonian Science 
Information Exchange. CCRESPAC also compiles these project descrip- 
tions into SPECIAL LISTINGS, which deal with some 60 specific 
research topics. The third data base, CLINPROT (CLINical Cancer 
PROTocols), contains about 1,000 summaries of clinical evaluations of 
new therapeutic agents and procedures. Although most of the protocols 
are supported by NCI's Division of Cancer Treatment, several hundred 
have been provided by other major American and foreign cancer centers. 

The growth of the CANCERLIT data base and the usage of 
CANCERLINE service are shown in figures 1 and 2. 

Cancer research information is actively disseminated to more than 
7,000 scientists through the ICRDB's Cancer Information Dissemination 
and Analysis Centers (CIDAC's). Three CIDAC's have been established. 
The CIDAC for Diagnosis and Therapy deals with information on cancer 
detection, diagnosis, treatment, rehabilitation, and other aspects of 
clinical oncology. The CIDAC for Carcinogenesis relates to chemical, 
environmental, and physical carcinogenesis, as well as cancer epidemi- 
ology. CIDAC for Cancer Biology covers the areas of biochemistry, 
cytology, genetics, immunology, virology, and other cancer-related 
disciplines. The information products of these facilities are actively dis- 
seminated by two major types of service. One is a monthly current 
awareness service known as CANCERGRAMS and the other is entitled 
ONCOLOGY OVERVIEWS. CANCERGRAMS are collections of ab- 
stracts of newly reported results in specific cancer research topics of 
special interest to research investigators. About 30 ONCOLOGY OVER- 
VIEWS are published annually. 

The ICRDB program also supports several specialized international 
projects to communicate information to scientists. An International 
Cancer Epidemiology Clearinghouse, funded jointly with the Interna- 
tional Agency for Research on Cancer (lARC) in Lyon, France, and the 



37 




OOOT 



93I^J.N3 






38 



m 



!r «^ t 

^ °^ 0^ 

O O Z 

Z 2 — 

^ < -J 

o o o 



o 

UN 



o 
o 

03 



O 




SbnOH iOlNNOO 



39 



German Cancer Research Center in Heidelberg, West Germany, publishes 
a recurring Directory of Ongoing Research in Cancer Epidemiology. 
The clearinghouse collects, processes, and disseminates detailed research 
data related to cancer epidemiology and studies of human cancer causa- 
tion in countries around the world. 

With the cooperation and support of the ICRDB program, the 
World Health Organization (WHO) has developed a series of publications 
on Tlie International Histologic Classification of Tumors, designed to 
facilitate worldwide adoption of a uniform and standard nomenclature 
for cancer. Collaboratively with ICRDB, the WHO has developed a 
coded nomenclature for neoplasms, the International Classification of 
Diseases for Oncology (ICD-0), which provides a detailed code for 
anatomic sites of neoplasms and their histopathology. The ICD-0 has 
been published in English, Spanish, and Portuguese; Russian, French, 
and German language versions are in preparation. The ICD-0 is designed 
to be used in tumor registries, cancer data banks, pathology laboratories, 
and departments of vital statistics so that data on cancer from different 
countries can be uniformly coded, reported, and analyzed. 

In collaboration with the Pan American Health Organization 
(PAHO), a Latin American Cancer Research Information Project 
(LACRIP) has been established. PAHO and its regional Library of 
Medicine (BIREME) identify, collect, and provide CANCERLINE with 
biomedical literature and summaries of active cancer-related projects in 
Latin America. PAHO serves as the coordinator for a series of clinical 
trials being conducted in eight Latin American cancer centers, each of 
which is linked with an American center, thus assuring that new tech- 
nology and clinical skills developed in the United States will be dis- 
seminated rapidly among the cooperating Latin American centers. 

Support is provided to the International Union Against Cancer 
(UICC) in Geneva which, through its Committee for International 
Collaborative Activities (CICA), assists the ICRDB in the collection and 
dissemination of cancer information throughout the world. CICA person- 
nel identify and promote collaborative projects among cancer centers 
and cancer specialists in different countries. CICA has published an 
International Directory of Specialized Cancer Research Treatment 
Establishments, containing descriptions of more than 700 cancer centers 
around the world. 

A partially ICRDB-supported center in Japan— the International 
Medical Information Center— coordinates the screening and collection of 
cancer-related information from Japan and Asian countries for entry 
into the CANCERLINE data bases. 

The availability of the CANCERLINE system and its use in devel- 
oping countries is being promoted through a contract with the British 
Library. This extension of the CANCERLINE service will enable scien- 
tists in some 100 developing countries to receive pertinent literature 
related to their cancer research efforts. They will also be in a position 
to keep abreast of recent advances in cancer research and cancer 
treatment. 



40 



Of significance is the recent collaborative effort of the ICRDB 
program and the UICC/CICA leading to the successful implementation 
of the International Cancer Patient Data Exchange System (ICPDES) oni 
a pilot-project scale. The ICPDES could result in the first internation- 
ally recognized and standardized tumor registry providing information 
on (1) cancer patient followup; (2) survival data; (3) demographic data; 
(4) comparisons and evaluations; and (5) eventual influence on treat- 
ment policy. 

Seven European cancer centers and four in the United States are 
participating in a project for the exchange of patient data. Two data 
centers, one in Europe and one in the United States, will store and 
analyze the data, currently dealing with four designated cancers: breast, 
colon and rectal, Hodgkin's disease, and larynx. As of June 1, 1978, the 
total numbers of eligible cases received per center are as follows: 







Cases 




Center 


Cases 


To Be Entered 


Total 


Brussels 


110 




110 


Rotterdam 


97 


161 


258 


Milan 


228 




228 


Budapest 


134 


212 


346 


Moscow 


131 


181 


312 


Bordeaux 


13 


146 


159 


M.D. Anderson 


362 




362 



1,775 



The cooperation of the Soviet Union as an active participant in 
this cancer data/information system is an encouraging sign. Up to this 
point, the Soviets have been reluctant to join the collaborative com- 
munication network established between the ICRDB program and 
other international institutions. 



Scientist-to-Scientist Communication 

A means for person-to-person communication between cancer 
researchers was implemented in 1975, with the acceptance of the UICC 
proposal to operate two major programs for an effective exchange of 
information between scientists in the international sphere. These are the 
International Cancer Research Technology Transfer (ICRETT) program 
and the International Cancer Research Workshop (ICREW) program. 

The ICRETT program provides awards to support brief research 
activities, usually not exceeding 3 weeks, to enable investigators from 
two different countries to work jointly on a problem of common 
interest or meet for intensive discussions^ and/or demonstrations on 
significant cancer technology. 



41 



The I CREW program provides partial support for workshops that 
bring together a small number (15 on the average) of cancer investi- 
gators from different countries, all of whom are working in the same 
field of basic, clinical, or behavioral research related to cancer. 

Since 1975, ICRETT program awards have been made available 
to some 250 individual scientists while some 50 workshops were spon- 
sored under the aegis of the ICREW program. From December 7, 1977, 
to mid-November 1978-the third year of ICRETT and ICREW-15 
workshops took place and some 120 ICRETT awards will have been 
made. 

Many of the recipients of ICRETT awards continue to collabor- 
ate on projects initiated during their visits to the laboratory of their 
host. As an example, an Argentine physician working in the area of 
experimental leukemias spent 3 weeks in the Institute for Scientific 
Research in Cancer, Villejuif, France. During the brief tenure, he was 
able to learn several operational steps necessary for somatic cell hybridi- 
zation and chromosome-gene transfer between cells. As a result of this 
exposure/training, he is now able to utilize these techniques in his own 
laboratory in Buenos Aires in analyzing tumor-tumor and tumor-normal 
cell hybrids. 

During a 2y2-week visit to the University of Texas Health Sciences 
Center at San Antonio, a Yugoslav scientist was able to compare his 
methods with those of his hosts for steroid receptor assay in breast 
cancer tissue. Because of this interaction, the visiting researcher was 
able to clarify some methodologic problems and technical difficulties he 
had been experiencing in his own laboratory. Exchanges such as this are 
extremely valuable for enabling investigators to standardize techniques 
and methodologies, thereby ensuring more precise interpretation of data 
from research in different laboratories on a common problem. 

A pathophysiologist from the NT Research Institute in Chicago 
was able to observe the histologic criteria used by Japanese researchers 
(Nagoya City University Medical School) for the classification of chem- 
ically induced tumors of the urinary bladder. 

The ICRETT and ICREW programs have been well received and 
are assessed as being scientifically rewarding. Acknowledgement of their 
value stems from the increasing number of applications in each succeed- 
ing year of the programs. The programs have been very successful in 
promoting and supporting the exchange of research information among 
scientists from various parts of the world and, in turn, have increased 
the opportunities for both formal and informal collaborative research 
activities on the causes, treatment, and prevention of cancer. Without 
these mechanisms for the exchange of cancer information, prevailing 
circumstances in the countries of some of the promising scientists might 
have delayed, by months, the opportunity for learning the most recent 
results in their fields of scientific endeavor. In slightly more than 2 
years, the ICRETT and ICREW programs have enhanced international 
communication in science and the promotion of important exchanges in 
science not covered by other research funding mechanisms. In several 



42 



instances significant contributions to the cancer literature have resulted 
from the exchanges. 



Bilateral Agreements 

The National Cancer Institute has been a party to formal and 
informal Bilateral Agreements since May 23, 1972, the time of the 
signing of the U.S.A.-U.S.S.R. Agreement for Cooperation in the Fields 
of Medical Science and Public Health. Subsequently, additional cooper- 
ative programs were initiated between the NCI and the Japanese Society 
for the Promotion of Science (1974); the Institute of Oncology of 
Warsaw, Poland (1976) as a segment of the U.S. A. -Polish People's 
Republic Agreement; the Cairo Cancer Institute (1976) under the aegis 
of the U.S. A. -Arab Republic of Egypt Agreement; the Ministry of 
Science and Technology of the Federal Republic of Germany (1976); 
and, in 1977, with the French Institut National de la Sante et de la 
Recherche Medicate (INSERM) under the earlier NIH Agreement with 
INSERM. 

In 1978, the NCI entered into its sixth bilateral association with 
the National Tumor Institute (Milan) and Institute of Experimental 
Oncology (Genoa) as part of the U.S. A. -Italian Republic Agreement 
entered into in 1977. Negotiations are in progress for still another 
cooperative program between the NCI and ine National Institute of 
Oncology (Budapest) under the auspices of the 1978 U.S. A. -Hungarian 
People's Republic Agreement. 



The U.S.-U.S.S.R. Agreement for Cooperation in 
the Fields of Medical Sciences and Public Health 

Six cancer problem areas are being studied jointly under the 
U.S.A.-U.S.S.R. Health Agreement: (1) cancer chemotherapy and com- 
bined modalities treatment; immunology; virology; somatic cell genetics 
related to neoplasia; cancer epidemiology; and methods of cancer con- 
trol and the role of cancer centers in cancer control, education, and 
training. 

During 1978, eight scientifically successful meetings of delegations 
or small working groups were conducted in the areas of cancer virology, 
mammalian somatic cell genetics, cancer epidemiology, and cancer 
control cancer centers. The total U.S.-U.S.S.R. cancer program was 
reviewed in the NCI in September 1978 and further scrutinized during 
Session Seven of the U.S.-U.S.S.R. Joint Committee for Health Cooper- 
ation in Moscow, October 1978. 

Forty-seven Soviet cancer specialists visited the United States in 
1978 and 25 American scientists were received in the Soviet Union. 
Some 51 person-months were devoted to these exchanges— 40 person- 
months by the Soviets and 1 1 by the Americans. 



43 



In cancer chemotherapy, the results of the study of 71 anticancer 
preparations were reviewed. The information from these data is the 
source for our second joint monograph, U.S.A.-U.S.S.R. Preclinical 
Anticancer Chemotherapy Test Data and Their Clinical Correlation. 
The English and Russian versions of the volume are scheduled for 1979 
publication. Ongoing projects in lung cancer were reviewed and agree- 
ment was reached to continue studies in the Soviet Union on the treat- 
ment of small-cell carcinoma and undifferentiated carcinoma of the lung. 
Th,e Soviets use combinations of American and Soviet nitrosourea deriva- 
tives, surgery, and radiation therapy. Our drug exchange to date has 
been highly productive— 166 anticancer and potential anticancer agents 
have been exchanged. Additional drugs have been considered for ex- 
change in 1979— three from the Soviets and four from the United States. 

During our Fifth U.S.A.-U.S.S.R. Oncology Program Review in 
September, the Soviet side summarized its work in cancer immunology 
on the immunotherapy of melanoma using BCG immunostimulation 
alone and in combination with surgery or with chemotherapy. Clinical 
trials, using four different protocols, have been completed and some 
significant results have been obtained. The Soviet studies confirm the 
results obtained in the United States, i.e., chemotherapy plus immuno- 
stimulation prolongs the time of melanoma remission. Long-term fol- 
lowup observations will continue. Trials are continuing in the U.S.S.R. 
using the protocol for C-parvum vaccine in breast cancer patients. New 
protocols for immunotherapy in various skin melanomas and lung cancer 
are under consideration. 

During their September meeting in Riga, American and Soviet 
virologists expressed satisfaction with their progress. Collaborative effort 
is continuing in seven topics on the identification, isolation, and charac- 
terization of viruses associated with certain cancers as well as those con- 
sidered to be potentially carcinogenic or playing" roles as cocarcinogens. 
From this research, two findings of significance have evolved: the 
isolation of a type C virus and the characterization of a type D RNA 
virus. These findings are detailed in joint scientific publications. 

The action on genetic systems of two anticancer drugs— 
5-fluorouracil (USA) and Ftorafur (USSR)— is being studied at the 
M.D. Anderson Hospital and Tumor Institute (Houston) and the Oncol- 
ogic Scientific Center (Moscow). Both drugs have comparable cytogen- 
etic activity in that they damage tumor cell chromosomes more 
significantly than they do chromosomes in normal cells. The exchange 
of biopsy specimens and cell cultures from tumors and rare genetic dis- 
orders predisposing to cancer is enabling American and Soviet geneticists 
to carry out complementary studies on the genetic basis of the disease 
from country to country. 

In cancer epidemiology, the success of the Harvard-Tallinn studies 
has encouraged American and Soviet scientists to continue work on 
the epidemiology of breast cancer with the expectation of developing 
additional data on high- and low-risk factors. Joint studies on the 
estriol-to-estrogen ratio in the urine of young women from Estonia are 



44 



nearing completion, and consideration is being given to including Geor- 
gian and Kazakh women. Plans for studies on the epidemiology of gyne- 
cologic cancer are under review in both countries. 

In cancer control and cancer centers agreement was reached on 
methods of classification and a unified terminology for describing non- 
infiltrated and infiltrated breast carcinomas. Risk factors in breast 
cancer were agreed to. The use of thermography for early detection was 
considered unreliable at this stage. Criteria for the use of film mam- 
mography were established. A uniform questionnaire and procedures 
have been developed for the study of breast cancer rehabilitation 
methods in 300 women in each country. Data collection is proceeding. 
Additional methods have been developed for analysis of data and evalu- 
ation of the end results of treatment of breast cancer patients. American 
and Soviet cancer centers with similar activities have been selected for 
studying the role of cancer centers in education of professional and pub- 
lic populations. 

The American-Soviet cooperative program in cancer affords an 
outstanding example of an interdisciplinary approach to dealing with a 
specific cancer site (figure 3). The insidious problem of breast cancer is 
being studied by American and Soviet cancer therapists, immunologists, 
virologists, epidemiologists, and cancer control specialists. Such a con- 
certed effort should pave the way for better methods of early detection 
of the disease, greater accuracy in diagnosis, more effective therapy, and 
elucidation of fundamental information that should ultimately bring 
about the control and/or prevention of the disease. 



Treatment Protocols 

Exchanged for 

Joint Study 



Polvchemotherapv 

+ Immunotherapy # ^5 
Trials 



CHEMOTHERAPY 



1547 Case-Control Analyses 
Estrogen Profile Studies 




Early Detection 
Rehabilitation 
Therapy Results 
Education 



Role of Viruses in 
Tumor Induction 



Figure 3. Breast cancer: interdisciplinary approach. 



45 



The Agreement Between the National Cancer Institute 
and the Japan Society for the Promotion of Science 

Since the inception c\ the U.S.A. -Japan Cooperative Research Pro- 
gram in May 1974, some 500 scientists from both countries have at- 
tended scientific and planning meetings, served as hosts to visiting 
delegations, or collaborated in laboratory projects. Conferences have 
been held on the causation of bladder cancer and on the comparative 
epidemiology of cancer in the United States and Japan. Nine other 
major areas of cancer are being explored. 

In the cancer immunology program area, a meeting on Immuno- 
therapy of Cancer and its Fundamental Basis resulted in an exchange of 
current information concerning clinical studies on immunotherapy and 
immunochemotherapy of cancer patients, using immilnopotentiators 
such as mycobacterium and its components. Fundamental studies on the 
mechanism of immunopotentiation were discussed. 

In the chemical carcinogenesis program area a 3-day symposium 
took place on the Role of DNA Repair and Misrepair in Radiation and 
Chemical Carcinogenesis in conjunction with the First International 
Radiation Biology Symposium on Molecular Mechanisms and Genetic 
Factors in Radiation Carcinogenesis. The scientific sessions were devoted 
to DNA repair defects in hereditary diseases with high incidence of 
cancer; genetic and epigenetic factors in radiation and chemical carcino- 
genesis; and inducible repair and misrepair in carcinogenesis and 
mutagenesis. 

Dialogue continues on the recent advances in both countries in 
the diagnosis and treatment of lung cancer. During the fourth joint 
symposium, topics discussed were (1) progress in morphology: the 
updated WHO classification of lung cancer, with special reference to the 
morphologic subtypes of small-cell and large-cell carcinoma; (2) advances 
in the Immunotherapy of lung cancer; (3) progress in the treatment of 
small-cell carcinoma, including multidisciplinary treatment methods; 
(4) treatment of non-small-cell lung cancer, both multidisciplinary treat- 
ment and chemotherapy; (5) indications for surgery in advanced lung 
cancer; and (6) cell kinetics and marker substances: their role for plan- 
ning and monitoring of therapeutic studies. It is anticipated that these 
discussions will lead to collaborative activities in lung cancer inasmuch as 
the incidence rates in both countries are increasing. Efforts in the future 
will include comparisons of data on clinical results. 

In the breast cancer program area, a meeting on Hormonal Recep- 
tors in Breast Cancer resulted in the exchange of data on the relation of 
hormones to breast cancer in two different population types. Significant 
differences were reported in the incidence and prognosis of breast cancer 
in each country. Japanese and American scientists discussed studies of 
hormone receptors in their respective populations and correlated these 
results with histopathology, free interval, and endocrine responsiveness. 
Similarities and differences were discussed regarding the subcellular 
biochemical pathways concerned with hormone dependence in the two 
patient populations. 



46 



In the exchanges on cancer virology, emphasis is placed on the 
nnechanism(s) of oncogenesis by DNA tumor viruses at the molecular 
and cellular levels of the host. Discussions focused on recent attempts to 
identify and to isolate the oncogenic fragments of the viral genomes and 
also on the function of their gene products. Information was exchanged 
on the correlation of the recent basic findings in virus research with 
efforts to determine the etiologic role of DNA viruses in certain types of 
animal and human neoplasias. 

Twelve Japanese and 10 American biostatisticians, epidemiologists, 
and cancer specialists met for a 4-day conference on the effective appli- 
cation of statistical methods to cancer research in order to promote the 
use of statistics in cancer research. The meeting was a success in that it 
brought together Japanese and American statisticians and epidemiologists 
to discuss mutual problems encountered in advancing the status of 
biostatistics and cancer epidemiology. During a joint symposium on 
cancer chemotherapy, discussions included (1) the design and methodol- 
ogy of phase I and II studies; (2) clinical evaluation of drug analogs; 

(3) clinical evaluation strategy in specific disease types, namely, lung 
cancer, breast cancer, gastrointestinal cancer and genitourinary cancer; 

(4) new drugs, including screening and development, and new drugs in 
clinical trials; (5) discussion on four classes of drugs, including nitro- 
soureas, bleomycin, anthracyclines, and fluorinated pyrimidines; and 
(6) joint cooperation on gastric cancer treatment protocols. 

The main purpose of the workshop on high LET radiation was to 
discuss the progress of ongoing cooperation in fast neutron radiotherapy 
and the development of common clinical trial protocols. Plans were 
advanced for investigations on the role of hyperthermia, use of radio- 
sensitizers, and other alternatives to high LET radiation therapy. 

The major highlight of the cytology program was the exchange of 
two senior pathologist-cytologist investigators. Each will spend an ex- 
tended period of time conducting joint research In the other's country. 

The Joint American-Japanese Steering Committee, during 1978, 
agreed to restructure the program to four major categories of cancer 
research: carcinogenesis, cancer biology and diagnosis, cancer treatment, 
and an interdisciplinary program. 



U.S. -Polish People's Republic Agreement 

Under the Agreement between the United States and the Polish 
People's Republic for Cooperation in the Field of Public Health, Amer- 
ican and Polish scientists visited the Institute of Oncology in Warsaw 
and the National Research Institute for Mother and Child for exchanges 
in pediatric oncology, radiation therapy, the leukemias, and carcinogen- 
esis. Polish scientists engaged in research training and cooperative re- 
search activities at several American cancer centers in fields that 
included biochemistry, endocrinology, epidemiology, pharmacology, and 
cancer treatment. 



47 



U.S.-Arab Republic of Egypt Agreement 

In the program sponsored by the National Cancer Institute and 
the Cairo Cancer Institute, Egyptian cancer specialists and NCI staff 
are working together on two bladder cancer progranns in which there is 
a relationship to bilharzial (schistosomiasis) infection among Egyptians. 
The joint study has established that the use of hexamethylmelamine 
reduces the size of the tumor for subsequent surgical intervention. 



NCI-Ministry of Science and Technology of Germany 

The program being developed under the NCI-German Ministry of 
Science and Technology Agreement has produced activity in the area of 
automated cytology technology for use in cervical cancer diagnosis and a 
potential application to the detection of cancers of the oral cavity. 
Negotiations are under way to expand this bilateral program to include 
(1) the testing of chemical carcinogens; (2) determination of the mech- 
anism (s) of action of carcinogenesis; and (3) study of the metabolism 
carcinogens. 



NCI-INSERM (Republic of France) Cancer Program 

Under the agreement with the Institut National de la Santa et 
de la Recherche Medicale of France, planning meetings have been 
held for collaborative research and for the exchange of scientists in 
the areas of viral oncology, hormone regulation in cancer, and treatment 
research. Collaborative experiments have been undertaken on topics such 
as cell transformation by viruses; the genetics of RNA tumor viruses; 
cellular antigens; hormonal regulation of receptor synthesis; pharma- 
cokinetic studies of 5-fluorouracil; and clinical trials using high dose 
methotrexate protocols, cis-platinum derivatives, FAM chemotherapy, 
and the combination of chemo- and immunotherapy. 



U.S.- Italian Republic Agreement 

The NCI and institutes of the Italian Ministry of Health will coop- 
erate in cancer treatment research (drug development and clinical trials), 
carcinogenesis, and epidemiology. 



U.S.-Hungarian People's Republic Agreement lOi 

The interest in joint efforts between the NCI and the Hungar- 
ian National Institute of Oncology includes experimental therapeutics. 



48 



experimental pathology, and immunology, with emphasis on leukemia 
and hematologic research. 



Informal Exchanges With the People's Republic of China 

In September 1977 there were 3 senior NCI scientists among 
the 11 Americans invited by the Committee on Scholarly Communi- 
cation with the People's Republic of China (PRC) National Academy of 
Sciences to visit various cancer research institutions and cancer hospitals 
in the PRC. During the 3-week visit, the American delegation had 
opportunities to discuss aspects of clinical treatment of various types of 
cancers, the epidemiology of cancer, and problems of basic research 
being supported in the cancer centers. 

Reciprocally, a delegation of 15 Chinese cancer specialists was 
hosted by the American Cancer Society in April 1978. The delegation 
visited several American cancer centers, in addition to spending 2 days 
at the National Cancer Institute. An extensive program on clinical and 
basic research in cancer was planned for the visitors, among whom were 
radiologists, epidemiologists, clinicians, and basic cancer specialists 
representing leading Chinese centers in Peking, Shanghai, and other 
cities. 

In the purview of the NCI, potential cooperation with the PRC in 
cancer studies could include (1) geographic epidemiology; (2) develop- 
mental therapeutics; (3) biochemical pharmacology and immunology; 
and (4) cancer biology, especially in vitro testing and somatic cell 
genetics related to neoplasia. 



Collaborative Research With Visiting Foreign Nationals 

As in previous years, the NCI Visiting Scientist Program has 
provided opportunities for young foreign scientists, as well as established 
researchers, to engage in cancer research with their American colleagues 
and share in their scientific experience. During the past year, the NCI 
hosted 155 visiting scientists representing 27 nations of the world. The 
majority of the visitors were young researchers who came to acquire 
advanced training and experience in the laboratories of senior NCI 
investigators. Eighteen foreign scientists were appointed as Experts, 
having obtained temporary senior positions for the conduct of inde- 
pendent research or for collaboration with senior NCI staff members on 
extant projects in their scientific specialties. Sixteen foreign scientists 
had temporary appointments as guest workers^ receiving financial sup- 
port from their home institutions or private or public foundations. 

Table 1 shows the number of such visitors and their countries of 
origin. 



49 



Table 1. Scientists From Foreign Nationals Visiting the NCI, FY 1978 



Countries of Origin 






Vi 


isiting Scientists 


Experts 


Guest Workers 


Argentina 








1 






Australia 








4 


2 


1 


Belgium 








4 


1 


1 


Brazil 








1 


-- 


- 


Bulgaria 








-- 


-- 


1 


Canada 








1 


2 


-- 


China, Republic of (Taiwan) 




4 


-- 


-- 


Egypt 








2 


-- 


-- 


Finland 








1 


-- 


-- 


France 








1 


-- 


-- 


Germany, Fed. Rep 


.of 






3 


-- 


1 


Greece 








2 


-- 


1 


Hong Kong, B.C. 








1 


1 


-- 


India 








21 


1 


1 


Ireland 








1 


-- 


-- 


Israel 








6 


-- 


-- 


Italy 








14 


-- 


-- 


Japan 








24 


3 


2 


Malaysia 








1 


-- 


-- 


Mexico 








1 


-- 


-- 


Netherlands 








2 


-- 


-- 


Poland 








1 


-- 


-- 


Portugal 








1 


-- 


- 


South Africa, Repul 


blic 


of 




1 


-- 


-- 


Spain 








1 


1 


1 


Switzerland 








3 


-- 


-- 


United Kingdom 








12 


3 


1 


Alien Residents or 1 


mm 


ligrants 




40 


4 


1 






Total 




154 


18 


11 = 183 



These activities have been most effective in the sharing of scien- 
tific information and the transfer of technology. Foreign scientists have 
been provided with unique opportunities for the development of a 
potential for sound research careers or improvement of existing skills in 
the scientific method. When a foreign scientist has been directly involved 
in NCI programs and has been exposed to disciplines involved in indi- 
vidual and coordinated projects, he is better equipped for solving prob- 
lems within his competence and has greater appreciation for the ex- 
pertise required to study the complexities of the cancer process. Close 
working contact between NCI scientists and those of foreign institutions 
will tend to improve and enhance technical and personal cooperation 
between individuals and groups. 



50 



International Contracts and Grants 

During FY 1978, the NCI awarded 92 contracts and 45 grants to 
principal scientists conducting basic and applied research in institutions 
of 20 nations of the world. The financial outlay of the NCI for these 
research activities is estimated to be about $13,500,000 of FY 1978 
funds, or approximately 1.5 percent of the NCI budget. Each of the 
projects supported in foreign countries is applicable and contributory to 
the goals of the NCI research thrusts. A profile of the NCI-supported 
international research and its emphasis is indicated by the following 
scientific disciplines: 

Biochemistry and immunochemistry 

Cancer biology 

Carcinogenesis 

Drug development 

Diagnosis 

Epidemiology 

Immunology 

Organ site cancers 

Treatment research 

Viral oncology 

Conference grants 

Information service 

Planning and development 

In the Division of Cancer Biology and Diagnosis emphasis is placed 
on fundamental immunology and immunotherapy. Research activities are 
related, in general, to the immune response to tumors, tumor antigenici- 
ty, drug-modified antigens, immunopotentiators, and cellular systems 
that might be established as biologic markers for a given cancer. The 
cancer problem areas, the number of projects/contracts, the funding per 
program area, and the distribution of contracts and funds per country 
are shown in table 2. 

Research being conducted for the Division of Cancer Treatment 
relates, principally, to the characterization of anticancer agents; the 
search for potential anticancer agents from natural sources such as 
microbial and plant; and the synthesis, screening, and testing of com- 
pounds developed in foreign laboratories. Clinical trials are conducted on 
specific cancers such as tumors of the brain. Support is provided for a 
WHO regional center in Milan, Italy, which coordinates clinical studies 
on the treatment of malignant melanoma, an effort involving a number 
of countries including the United States and the Soviet Union. The 
fields of emphasis and distribution of NCI resources toward foreign 
research in cancer treatment are shown in table 3. 



51 



Table 2. Division of Cancer Biology and Diagnosis Contracts 
to Foreign Institutions, FY 1978 



Program Areas 



No. of Contracts 



Total Amounts 



Immunology 
Cancer biotogy 
Breast cancer 



23 

7 

_3 

33 



$1,403,746 
566,654 
178,937 

$2,149,337 



Countries 



No. of Contracts 



Total Amounts 



Australia 

Austria 

Finland 

Israel 

Italy 

Netherlands 

Sweden 

United Kingdom 

West Germany 



3 
2 
4 
13 
1 
2 
4 
3 
1 

33 



$ 



188,781 

117,000 

167,080 

1,047,097 

67,000 

51,275 

235,000 

205,113 

70,991 



$2,149,337 



Table 3. Division of Cancer Treatment Contracts 
to Foreign Institutions, FY 1978 



Program Areas 



No. of Contracts 



Total Amounts 



Drug development 
Treatment research 
Drug research 



8 
9 
1 

18 



$ 945,187 
703,135 
304,430 

$1,952,752 



Countries 



No. of Contracts 



Total Amounts 



Belgium 

Canada 

Italy 

Japan 

Netherlands 

Uganda 

United Kingdom 



2 
2 
6 
2 
1 
1 
4 

18 



$ 260,760 
298,742 
729,246 
199,000 
73,151 
25,000 
366,853 

$1,952,752 



52 



Foreign research activities in carcinogenesis, cell biology, epidemi- 
ology, and virology-genetics are of relevance to the research thrusts of 
the Division of Cancer Cause and Prevention (DCCP). Importance is 
ascribed to enzyme-induced chemical carcinogens, N-nitroso compounds, 
and the poly cyclic hydrocarbons, respectively, in these areas. Informa- 
tion is needed on the preservation of biochemical mutants, mammalian 
transport systems, and tissue interacting factors. Morbidity surveys, case 
control studies, seroepidemiology, risk data, and cancer incidence rates 
in countries other than the United States are essential. Knowledge is 
required on the induction of genetic aberrations and their possible 
relationship to cancer as well as the role of viruses as suspect or poten- 
tial carcinogens. The effort of DCCP with scientists in foreign laborator- 
ies is summarized in table 4. 



Table 4. Division of Cancer Cause and Prevention Contracts 
to Foreign Institutions, FY 1978 



Program Areas 


No. 


of Contracts 


Total Amounts 


Carcinogenesis 




20 


$2,437,196 


Epidemiology 




7 


865,569 


Cancer biology 




1 


83,000 


Pharmacology 




1 


85,000 


Immunology 




1 


49,500 


Viral oncology 




4 


785,270 






34 


$4,305,535 


Countries 


No. 


of Contracts 


Total Amounts 


Canada 




4 


$ 441,016 


Colombia 




2 


213,514 


Israel 




5 


813,921 


Italy 




1 


85,000 


Japan 




3 


162,704 


Netherlands 




3 


312,500 


Norway 




1 


7,800 


Sweden 




2 


392,000 


United Kingdom 




7 


512,377 


West Germany 




1 


108,120 


International Agency (lARC) 


_5 


1,256,583 






34 


$4,305,535 



The contracts effected through the Office of the Director, NCI, 
are listed in table 5. Five of the seven projects relate to the ICRDB 
program. 



53 



Table 5. Office of the Director Contracts 
to Foreign Institutions, FY 1978 



Program Areas 



No. of Contracts 



Carcinogenesis 1 

Epidemiology 1 

Information science 4 

Planning and development 1 



Total Amounts 

$ 150,000 

1 1 5,049 

973,997 

1,418,869 







7 


$2,657,915 


Countries 


No. 


of Contracts 


Total Amounts 


Japan 




1 


$ 150,000 


United Kingdom 




2 


1,578,869 


lARC (France) 




2 


265,049 


UICC (Switzerland) 




2 


663,997 



$2,657,915 



Table 6 provides similar data on the number of research grants 
awarded to scientists in foreign countries for meritorious studies in areas 
of interest to the NCI and its mission. 



Table 6. NCI Research Grants to Foreign institutions, FY 1978 



Program Areas 


No. of Grants 


Total Amounts 


Cancer biology 


3 


$ 156,924 


Carcinogenesis 


6 


262,433 


Diagnosis 


1 


15,401 


Drug development 


2 


46,255 


Treatment research 


14 


809,741 


Epidemiology 


1 


24,600 


Immunology 


11 


673,557 


Pharmacology 


1 


47,555 


Viral oncology 


4 


154,715 


Conference grants 


2 


131,162 




45 


$2,322,343 



54 



Countries 

Australia 

Belgium 

Canada 

Denmark 

Finland 

France 

Israel 

Japan 

Korea 

South Africa 

Sweden 

United Kingdom 

West Germany 

UICC (Switzerland) 



No. of Grants 


Total Amounts 


4 , 


$ 164,395 


1 


298,286 


14 


574,785 


1 


39,400 


1 


38,000 


1 


50,000 


8 


387,058 


1 


45,024 


1 


11,005 


1 


72,397 


2 


230,358 


7 


238,882 


2 


73,411 


1 


99,162 


45 


$2,322,163 



The relationship with international institutions and organizations 
and their scientists has been mutually advantageous in providing oppor- 
tunities for furthering our understanding of the causes of cancer, its 
treatment, and its control and/or prevention. Certainly, the expertise of 
foreign researchers and the results of their investigations are relevant to 
the NCI goal of improving cancer treatment and significantly reducing 
the incidence of human cancer. 



Summary 

The foregoing description of the international activities of the 
National Cancer Institute delineates the NCI impact on the effort against 
cancer by a seeming consortium of nations. Reciprocally, those nations 
collaborating with the NCI in the "war on cancer" are making signifi- 
cant contributions to the missions of the NCI for the peoples of Amer- 
ica. Advancing the thesis of international cooperation a bit further, the 
products of this research effort are being applied toward the improve- 
ment of cancer care mechanisms or systems in those countries where the 
socioeconomic environment seems to preclude such advances through 
autonomous research endeavors. By continuing, and even expanding, its 
role in collaborative international research, the NC! will understand 
better the relationship between cancer patients of the world and the 
differing biologic, economic, sociologic, and technologic conditions 
that impinge upon their immediate being. As each new piece of informa- 
tion is added to existing knowledge related to the cancer-disease- 
complex, its cure and prevention could be accelerated. This becomes 
even more pragmatic when we consider that a disease is a biologic 
aberration— abnormal alterations in a cell, a molecule, an organ, or an 



55 



entire physiologic system. A disease, therefore, can be understood in 
scientific and objective terms. But the changes in biologic processes 
that create the disease, cancer, are not fully understood. Thus, it is 
mandatory that the momentum continue. Eventually, early detection 
will be possible, more efficient controls and/or cures will be instituted 
and, ultimately, prevention may be possible. 



National Eye Institute 



introduction 

The National Eye Institute conducted an active international pro- 
gram in FY 1978. Essentially the Institute's international activities fall 
into two categories: (1) the conduct of research by investigators around 
the world where high level expertise is available and unique research 
opportunities exist; and (2) the provision of advice and consultation to 
various U.S. Government agencies, such as the Office of International 
Health, PHS; the Office of the Secretary, HEW; the Agency for Inter- 
national Development; and the State Department, concerning eye disease 
and the prevention of blindness. As one of the few sources of expertise 
in eye disease and eye care in the U.S. Government and certainly the 
principal referral point for this information, the National Eye Institute 
is frequently called upon by other Government agencies. 



Background 

Part F, Section 453 of the Public Health Service Act provides the 
following legislative mandate to the Secretary, HEW: 

The Secretary shall, through the National Eye Institute 
established under this part, carry out the purposes of Section 
301 with respect to blinding eye disease and visual disorders 
associated with general health and well-being, including the 
special health problems and requirements of the blind and 
the mechanism of sight and visual function. 

In FY 1978, the National Eye Institute direct budget for inter- 
national activities was: 

Research Grants $500,000 

Direct Consultations $ 25,000 



56 



Major Programs and Activities 

On May 2, 1978, President Carter made the following official 
statement regarding international health: 

We will put special emphasis on providing clear drinking 
water, basic sanitation, basic immunizations and efforts to 
prevent and treat blindness. 

Secretary Califano of HEW followed up on this Presidential prior- 
ity with the following message to the World Health Assembly meeting 
in May 1978 in Geneva, Switzerland: 

We will support worldwide efforts to prevent and treat 
blindness. The stark fact is that 80 percent of blindness is 
preventable or curable. But unless we can expand prevention 
and treatment programs, the number of blind people 
throughout the world will continue to increase ... 

The National Eye Institute has been requested by the Office of 
International Health, HEW, and the Fogarty International Center, NIH, 
to lend its expertise to shaping U.S. efforts that will lead to the realiza- 
tion of the objectives contained in these two statements. Additionally, 
the NEI in carrying out its basic mission in vision research is supporting 
a number of vision research projects around the world on an individual 
basis and through bilateral agreements with foreign countries. During 
FY 1978, NEI engaged in the international programs summarized below 
by program area. 



Collaboration and Consultations With the 
World Health Organization (WHO) 

The Director, National Eye Institute has been appointed as a 
member of the WHO Programme Advisory Group for the Prevention of 
Blindness. The major aims of this group are to advise ori the development 
of a program including priority setting, project evaluation, and consultant- 
ships. In establishing a separate Programme for the Prevention of Blind- 
ness on January 1, 1978, WHO has made a major commitment to serve 
as promoter, or catalyst, for national and local efforts to alleviate the 
overburden of world blindness. The WHO activity is directed at: 

1. Assessment of nature and extent of the problem; 

2. Formulation of national or regional plans, programmes and 
projects; 

3. Collection, collaboration, and distribution of relevant data; 

4. Organization and management of training activities such as 
seminars, meetings, training courses, including the preparation 
and provision of teaching aids; 



57 



5. Advisory services by short-term consultants, and possibly of 
personnel for longer periods. 

Additionally, in FY 1978 the Director, NEI, participated as an 
official member of the U.S. delegation to the annual World Health 
Assembly of the WHO. Discussions and consultations with health minis- 
ters of many countries and WHO officials were held regarding the 
development of prevention of blindness activities. 



Future Plans 

The Institute plans to continue active collaboration and participa- 
tion in the WHO Programme for the Prevention of Blindness. In 1979 it 
is expected that the NEI will provide modest funding to WHO for the 
support of projects aimed at 

1. Obtaining sound epidemiological data on the prevalence of 
visual impairment and blindness from all causes; 

2. Evaluating available health technologies and promoting pro- 
grams to make the most cost/effective of these available to 
affected populations; and 

3. Stimulating programs of research into blinding eye diseases for 
which there is no known satisfactory treatment and controlled, 
clinical evaluation of findings which appear to be effective. 

Finally, the NEI intramural program in Bethesda is making plans 
to be designated as a WHO collaborating center. 



International Agency for the Prevention of Blindness 

During 1978, the National Eye Institute continued its cooperative 
efforts with the International Agency for the Prevention of Blindness 
(lAPB). The lAPB's mission is to spread the message of the extent and 
distribution of world blindness, particularly to developing nations, since 
most preventable blindness occurs in these nations. Developed nations 
can provide resources and expertise to prevent world blindness and im- 
prove their own prevention activities. Most importantly, the lAPB must 
create the will for these nations to act in their own behalf and for the 
benefit of people everywhere who are potential victims of avoidable and 
curable blindness. Private voluntary U.S. organizations that are members 
of the lAPB are the Helen Keller Institute, the National Society to 
Prevent Blindness, and the International Eye Foundation. Over 47 
countries have national committees that are members of the lAPB. 

National Eye Institute staff participated in the First General 
Assembly of the International Agency for the Prevention of Blindness 



58 



held in Oxford, England, on July 8, 1978. The assembly was highly 
successful in promoting international interest and support for attacking 
the world s major causes of blindness. 



FY 1979 Plans 

The NEI will continue to serve as an active participant in this 
organization and encourage private U.S. voluntary organizations to play 
a more active role in this group. 



U.S.-U.S.S.R. Collaboration 

Under the U.S.-U.S.S.R. Medical Science and Public Health Agree- 
ment, vision research has been recently assigned the same high priority 
as afforded other major ongoing U.S.-U.S.S.R. collaborative health 
research efforts in cancer, cardiovascular diseases, artificial heart, envir- 
onmental health, schizophrenia, arthritis, and influenza and acute res- 
piratory diseases. This collaboration was initiated a few years ago by an 
exchange of visits between the Director, NEI, and Dr. Mikhail M. Kras- 
nov. Director of the All-Union Scientific Research Institute of Eye 
Diseases of the Soviet Ministry of Health. Subsequent informal contacts 
by Drs. Kupfer and Krasnov have resulted in identifying specific research 
projects and scientists who would initially participate in a vision research 
exchange program. Detailed plans were developed at the Seventh Session 
of the U.S.-U.S.S.R. Joint Committee for Health Cooperation held 
recently in Moscow. These call for initial projects in laser treatment of 
glaucoma, in research on retinal degenerations, and in studies of cataract. 

Also in FY 1978, Dr. Elmer Ballintine, Clinical Director, NEI, 
attended a symposium in the U.S.S.R. on "The Pathogenesis and Treat- 
ment of Hereditary Tapetoretinal Dystrophies" under the individual 
exchange program of the U.S.-U.S.S.R. Medical and Public Health 
Agreement. Presentations concerning a new treatment for Retinitis 
Pigmentosa (RP) with a drug called ENCAD were of particular interest. 
RP, an important cause of visual disability and blindness, has a devas- 
tating impact early in life on those afflicted. In general, the results 
showed that, despite years of testing in the U.S.S.R., ENCAD's benefits 
are inconclusive. Individual case ret)orts of improvement following treat- 
ment were unconvincing. 



International Vitamin A Research Center 

A workshop held at the NEI in FY 1977 recommended that the 
Institute pursue several high-priority research opportunities concerning 
the relationship of vitamin A to malnutrition blindness, a serious prob- 
lem in developing countries. During the past decade, many governments 



59 



throughout the world have expended significant time and money in 
distributing vitamin A capsules to combat malnutrition blindness (pri- 
marily xeropthalmia and keratomalacia) diseases that severely affect the 
cornea and are a leading cause of visual impairment and blindness 
worldwide. Recently vitamin A food supplementation also has been 
used. Yet the value of these approaches has not been scientifically vali- 
dated. Very little reliable research data exist on such subjects as: (1) the 
interdependence of protein supplementation and vitamin A utilization; 
(2) the best dosage to increase vitamin A blood levels; (3) the most 
effective approach to increasing retinal-binding protein in the serum of 
malnourished children; and (4) the possible role of collagenase in kera- 
tomalacia. Despite the scientific information available on the biochem- 
istry and physiology of vitamin A in the normal individual, little is 
known about vitamin A in the protein/calorie deficient child. 

The Office of Nutrition in the Agency for International Develop- 
ment is interested in supporting the establishment of a research center 
to reinforce the following NEI workshop research opportunities: 

1. Epidemiology — the relationship of vitamin A deficiency and 
protein/calorie malnutrition to keratomalacia/xerophthaimia and 
diarrheal disease in populations at risk. 

2. Diagnosis — morphological studies of the effects of vitamin A 
deficiency on the cornea. Surprisingly, no such studies have yet 
been conducted. 

3. Nutrition — studies of how carotene and retinol are absorbed 
in affected children with protein/calorie deficiency. 

4. Biochemistry — a wide range of studies of the biochemistry of 
vitamin A in affected patients; e.g., the biochemistry of tissue 
vitamin A receptors, glycoproteins of the cornea, estimation of 
liver vitamin A stores, etc. 

5. Prevention/Treatment — the best and most cost effective 
method of rapid vitamin A therapy and of long-term control 
through treatment, nutrition and education. 

To carry out this research, the consultants recommended that a 
center be established for study of keratomalacia in an area of high pa- 
tient density and, if possible, in conjunction with an already ongoing 
program. Two possible locations for the center are Dacca, Bangladesh, 
and San Salvador, El Salvador. At least one other country will be visited 
before a final decision is made. 



U.S.- J apart Cooperative Agreement 

The U.S. -Japan Memorandum of Understanding (MOU) on Vision 
Research became effective April 1, 1976, for 3 years. The MOU provides 
for an exchange of scientists program sponsored by the National Eye 
Institute and the Japan Society for the Promotion of Science. Two 



60 



scientists per year from each country may be selected for the exchange- 
one short-term (2 weeks to 3 months) and one long-term (3 months to 
1 year). Plans are under way to renew the U.S.-Japan Cooperative 
Agreement for a second 3-year period. 

The MOD objectives are to foster better communication and inter- 
action between Japanese and U.S. vision research scientists; to broaden 
the base of vision research through cooperative efforts; and to better 
utilize existing resources for vision research in both countries. 

During 1978, Dr. Thomas G. Ebrey spent 3 months at Kyoto 
University studying the retinal-protein interaction in visual pigment and 
the analogous pigments; Dr. Mitsuo Ikeda spent 3 months visiting several 
laboratories throughout the United States pursuing his studies into 
physiological optics and visual information processing, specifically in the 
field of visual pattern perception, color vision and visual sensitivity; and 
Dr. Naohiro Ishii is spending the better part of 1 year at the Brain 
Research Institute of the University of California studying analysis and 
information processing of electrical activity of the brain, pattern recog- 
nition, and cybernetics. 

In FY 1978, Dr. Kanjiro Masuda spent 1 year at Yale University 
working in uveitis research, and Dr. Motohiko Murakami spent 3 months 
visiting several laboratories across the United States teaching a new 
technique in micro-electrode methods. Also, Dr. Duco Manasaki from 
the Bascom Palmer Eye Institute spent 1 year at the Tohoku University 
working in the area of retinal protein interaction in visual pigment and 
analogous pigments. Dr. William H. Miller spent 2 weeks visiting the 
St. Marianna University and the Iwate University lecturing on factors 
influencing visual acuity in the retinas of man and birds and on struc- 
tures with dimensions near wavelengths of light as intraocular filters. 

Today as many as 40 million people are blind. There is a critical 
need and well-established opportunity to prevent or treat much of this 
blindness. The National Eye Institute can play an important role in pro- 
viding technical and medical advice to the U.S. Government's policy- 
makers concerning the desirability and possible nature of U.S. participa- 
tion. Also, the NEI can help insure that the most cost-effective new 
approaches are utilized in an international program for the prevention of 
blindness by evaluating new technologies and conducting clinically rele- 
vant research. 



National Heart, Lung, and Blood Institute 



Introduction 

The National Heart, Lung, and Blood Institute's international 
programs and activities represent an undertaking in the best tradition of 
medicine which recognizes no national boundaries in Its quest for 



61 



relieving human suffering. During FY 1978, the Institute continued to 
expand its international activities and contacts, and a series of meetings 
were held with officials from other countries to explore new opportuni- 
ties of mutual interest. 

The problems of heart, blood vessel, lung, and blood diseases and 
problems related to blood resources are not unique to the United 
States. They are shared to a greater or lesser degree by all nations, 
industrialized as well as developing countries. Table I shows selected 
statistics comparing the United States with other countries in terms of 
trends in cardiovascular disease, the number one cause of death. 



Table 1. Trend in the Death Rate for Coronary Heart Disease 

Selected Countries, 1969-73 

Males Age 45-54 Years 

Country Difference in Death Rate Rate Per 100,000 Population 



United States (white) - 28,3 



Finland 


- 


17.1 


Austria 


- 


0.4 


Italy 


-1- 


0.6 


Netherlands 


+ 


2.5 


Switzerland 


+ 


4.1 


German Fed. Rep. 


+ 


9.3 


Hungary 


+ 


21.5 


Sweden 


+ 


30.1 


Norway 


+ 


31.1 


England and Wales 


+ 


31.6 


Denmark 


+ 


31.9 


Northern Ireland 


+ 


43.2 


Scotland 


+ 


43.5 



1969 


1973 


341.2 


312.9 


427.3 


410.2 


146.7 


146.3 


112.9 


113.5 


188.8 


191.3 


103.4 


107.5 


146.4 


155.7 


142.8 


164.3 


126.0 


156.1 


191.5 


222.6 


254.9 


286.5 


159.5 


191.4 


318.9 


362.1 


329.2 


372.7 



A highlight of 1978 that has gained worldwide attention is the 
Institute's report on the significant decline in the previously unchecked 
epidemic of U.S. deaths from cardiovascular disease (figure 1). This has 
occurred in both of the major categories: heart attacks and stroke. This 
decline is steeper than that for other diseases. It is particularly note- 
worthy in view of the increases in cardiovascular death rates for most 
other nations, industrialized and developing, over the same period of 
time. At a recent conference on the decline in cardiovascular deaths, 
it was predicted that the death rate from heart and artery disease could 
be cut in half by the year 2005. There is reason to believe that the 
National Heart, Blood Vessel, Lung, and Blood Program mandated by 
the President and Congress in 1972, and implemented by the Institute, 
has played a pivotal role in bringing about these positive trends in the 



62 



•— CN 







in 














0) 


























(D 


cc 


CD 


0) 


in 


^ 


>- CO 


+-* 






3 
CD 


T— 


'S-' 


r-' tt 


o 


^ 


^ 


'J- 


CO 


O CN 


h- 


to 


U 


CO 


CD 


CN 




0) 










1 1 




Q 


















Q 














> 


a> 


CN 


P- CN 








IT) 


oi 


CD 00 








c 


V— 


fO 


r~ t- 








o 


t 


CO 










Z 






1 1 




•(- 


Q 


CO 


CM 


tT CD 






-w 


tri 


iri 


d d 






<D 


> 


CN 


o> 


CO CO 






QC 


U 


t 


CN 


1 1 














05 CU 














(3) O) 










o 


CO 


C C 








l_ 


IT) 


r^ 


(D CD 








03 


Oi 


CD 


JZ r. 








> 









s 



T- «- r>4 



63 



health of the people of the United States. In 1978 alone 200,000 nnore 
heart deaths would have occurred, had death rates stayed at the same 
level as in 1968. 

The experience of the United States has stimulated other nations 
to try to duplicate the positive results achieved in our country. Many of 
the Institute's joint meetings with international scientists during the past 
year focused on how the Institute can best collaborate with other 
nations to bring about similar results while at the same time obtaining 
new knowledge about the relative contributions of specific factors in 
causing the changes observed in the United States. This knowledge will 
be valuable in further accelerating positive trends in the United States. 
There is still far to go before the United States approaches the much 
lower cardiovascular death rates of nations such as Japan, Italy, and 
Yugoslavia. 

Developing countries are also interested in stemming the epidemic 
of heart and artery disease before it becomes a major economic and 
health problem. This interest is evident from the requests for advice 
received by the Institute in FY 1978. International trust in the Insti- 
tute's approaches and programs is also exemplified in the appointment 
of the Director, National Heart, Lung, and Blood Institute, as adviser to 
the World Health Organization (WHO) in the development of long-range 
programs in cardiovascular disease. 

The decline in cardiovascular death rates in the United States has 
been attributed to a number of factors. The relative roles of these fac- 
tors are currently under study. Eating and smoking habits of Americans 
changed considerably during the past decade. A new emphasis on hyper- 
tension control was also initiated. The per capita consumption of eggs, 
milk-fat products, and lard declined significantly as Americans sought to 
avoid foods containing cholesterol. At the same time there was a decline 
in the amount of tar and nicotine in cigarettes and a 25 percent reduc- 
tion in male smokers in all age groups 21 and over in the period 1964 
to 1975. 

During the past year scientists from other nations showed particu- 
lar interest in joint international activities related to the so-called major 
cardiovascular risk factors: hypertension, hyperlipidemia, and smoking. 
"Hypertension Etiology, Treatment, and Prevention" was approved as a 
new program area within the U.S.-U.S.S.R. joint exchange in cardiovas- 
cular diseases. The collaboration was initiated with a Joint U.S.-U.S.S.R. 
Symposium on Hypertension held in Sochi in June 1978. A Joint 
U.S.-F.R.G. Memorandum of Understanding was signed with the Federal 
Republic of Germany for collaboration on hypertension and arterio- 
sclerosis. A Joint U.S.-F.R.G. Workshop on Hypertension and Arterio- 
sclerosis was held in Heidelberg in August 1978, with followup 
discussions in Bonn with representatives from the three government 
agencies responsible for relevant health research programs. Representa- 
tives from F.R.G. have requested U.S. collaboration in developing and 
sharing data on epidemiological studies and risk factor intervention 



64 



programs. A Joint Memorandum of Understanding was also negotiated 
with tine Republic of Italy for joint collaboration on the prevention of 
heart disease. Followup planning meetings were held for a Joint U.S.- 
Italian Workshop on "Cardiovascular Risk Factors" in Rome in Decem- 
ber 1978. 

During FY 1978, the National Heart, Lung, and Blood Institute 
continued programs of joint collaboration with the Soviet Union in the 
seven previously approved program areas. Collaborative activities con- 
tinued with scientists in Israel, Yugoslavia, Poland, Great Britain, France, 
Egypt, Japan, and WHO representatives. The Institute also funded a 
number of fellowships, contracts, and research grants to investigators in 
other countries and received visiting scientists from many nations. 



Major Programs and Activities 

The Institute's international programs and activities are carried 
out within the Institute's mandates under the National Heart, Lung, and 
Blood Program. There is no separate legislative authority for these 
activities beyond those governing HEW and PHS operations, nor is 
there a separate budget line item for international programs. Operating 
funds from the Office of the Director, NHLBI, are used for international 
programs. Funds may also be drawn from line research budget categor- 
ies, depending upon the project. 

The direct costs for NHLBI international activities are summarized 
in table 2. Under the bilateral agreements, each side pays for the travel 
of its scientists to the other country. The receiving country pays all 
expenses for U.S. scientists traveling within the host country and for the 
facilities, personnel, equipment, and supplies needed for joint studies. 
The U.S. side pays for reciprocal arrangements within the United States. 



U.S.-U.S.S.R. Health Exchange in the Cardiovascular Area 

A Joint U.S.-U.S.S.R. health exchange in Cardiovascular Diseases 
was initiated in 1972 through a bilateral health agreement signed by the 
U.S. Secretary of State and the U.S.S.R. Minister of Health. The agree- 
ment was renewed in 1977 for 5 years. 

Four areas of joint collaboration were approved by the U.S.- 
U.S.S.R. Joint Committee in 1972: Pathogenesis of Arteriosclerosis; 
Management of Ischemic Heart Disease; Myocardial Metabolism; and 
Congenital Heart Disease. Two additional areas were approved in 1973: 
Sudden Death; and Transfusion of Blood, Its Components, and Pre- 
vention of Hepatitis with Particular Reference to Cardiovascular Surgery. 
A seventh area was added in 1978: Hypertension Etiology, Treatment, 
and Prevention. Cooperation on Artificial Heart Research and Develop- 
ment was initiated in 1974 under a separate agreement signed by Kissin- 
ger and Gromyko. This agreement was also renewed in 1977 for 5 
years. 



65 



Table 2. National Heart, Lung, and Blood Institute 
International Activities 
Direct Costs FY 1978 



Total Awards 

Bilateral 
Agreements* 



23 



Funds expended in 
the United States 



Funds Paid 





Number 


Countries 


(in dollars) 


Fellowships 


3 


Canada 
Sweden 
France 


39,776 


Contracts 


12 


Canada 

United Kingdonn 
Israel 


2,554,371 


Grants 


8 


Argentina 
Canada 
Denmark 
Sweden 


349,540 






United Kingdom 





2,943,687 
420,642 



^Collaborating countries pay for costs in their own country. 



Heart disease is the principal cause of death in both the Soviet 
Union and the United States. It is an area of intense public and scien- 
tific interest in both countries. Significant progress was made during 
FY 1978 in terms of further developing joint areas of research, resulting 
in exchange of information and data, and publication of papers on 
joint research. 

During the past 6 years of cooperation, the total number of 
individuals exchanged in the eight cardiovascular areas was 339" 214 
U.S. and 125 U.S.S.R. specialists. The total number of man-months was 
237, counting one man-month as 30 days exchange in either country: 
113 for the U.S. and 124 for the U.S.S.R. More than 100 U.S. and 
Soviet institutions have participated in the exchange, more than 60 in 
the U.S. and more than 40 in the U.S.S.R. Ten joint symposia were 
held. The proceedings of nine symposia were published (or are in press) 
in English and in Russian. The proceedings of the latest symposium, 
held in June 1978, are being prepared for publication. A total of more 
than 300 scientific reports, abstracts, and related articles have been 
published under the aegis of the joint U.S. -U.S.S.R. exchange in the 
cardiovascular area. 

Pathogenesis of Arteriosclerosis. Arteriosclerosis, the subject of 
joint epidemiological studies in area 1 of the Cardiovascular Exchange, 



66 



is the most common cause of cardiovascular disease. Directly or indirect- 
ly it is responsible for more deaths in the United States and the Soviet 
Union than any other disease. 

The U.S. -U.S. S.R. Lipid Research Clinics (LRC) program is a 
unique endeavor in conducting a binational multidisciplinary, multi- 
clinic collaborative research program. This program particularly focuses 
on the metabolism and epidemiology of plasma lipids and lipoproteins 
as they relate to the atherosclerotic disease in total populations. During 
FY 1978 this program maintained its well established high level of suc- 
cess. Some of the results of the joint studies have been published and a 
number of joint publications are in preparation. Two joint working 
meetings and two joint steering committee meetings were held in 
FY 1978. 

The initial agreement stated that the U.S. -U.S. S.R. study would 
include men between the ages of 40-59 years. This study has now been 
completed and the joint analysis is in progress. On the U.S. side, the 
Lipid Research Clinics program studied approximately 33,000 individuals 
during the initial phase (phase 1) of the study and about 4,000 in the 
second, more specialized phase (phase 2). On the U.S. S.R. side, 8,000 
individuals were studied in Moscow and Leningrad during phase 1, and 
approximately 2,000 during phase 2. 

Interesting new biochemical data have been generated as a result 
of the cooperation. Last year significant differences were discovered 
between populations studied in Leningrad and the United States, especi- 
ally in the blood levels of high density lipoproteins. During FY 1978 
these findings were further delineated. This is an important area of new 
research which has a following the world over. The reason for the inter- 
est in high density lipoprotein is that high levels of this lipoprotein are 
generally associated with longevity and decreased risk of heart disease. 
The U.S. levels of this lipoprotein are lower than those in Leningrad 
and, to a lesser extent, than those in Moscow. The findings may have 
implications for the U.S. -U.S. S.R. joint effort to lower the risk factors 
in arteriosclerosis. 

Important new findings from the U.S. -U.S. S.R. joint studies in 
the LRC's were reported at the U.S. -U.S. S.R. Joint Symposium on 
Hypertension in Sochi in June 1978. The data show that, in the popu- 
lations studied, U.S. S.R. men ages 40-59 have higher levels of blood 
pressure than U.S. men of comparable age. The prevalence of high blood 
pressure was two to three times greater in U.S. S.R. than in U.S. white 
men. Also, the prevalence of hypertension was higher in hyperlipidemic 
men than in random sample examinees in both the U.S. and U.S. S.R. 

During FY 1978, agreement was reached on a mortality followup 
study of men ages 40-59 years screened during phase 2 of the original 
joint study, and a sample of those screened during phase 1. Agreement 
was also reached on expanding the U.S. S.R. prevalence studies to other 
population groups including men and women, ages 20-69, residing in 
districts of Moscow and Leningrad other than those included in the 
earlier joint studies. Also, plans are under way for a Joint U.S. -U.S. S.R. 



67 



Symposium on High Density Lipoproteins to be held in the Soviet 
Union. The inclusion of a third U.S.S.R. Lipid Research Clinic in Kiev is 
receiving serious attention. 

Management of Ischemic Heart Disease. Ischemic heart disease 
(IHD), the subject of joint clinical studies in area 2, is the most com- 
mon cause of death in the United States and the Soviet Union. It is 
responsible for chronic illness and disability of many millions of U.S. 
and Soviet citizens. Improved treatment for IHD is therefore an urgent 
nped in both countries. 

The joint U.S. -U.S.S.R. study in the management of ischemic 
heart disease is an evaluation and comparison of new modes of therapy 
as opposed to standard medical practice, as well as an assessment of 
their appropriate roles in modern medical management. In the United 
States, the surgical technique under study uses a blood vessel graft to 
bypass a narrowed or occluded segment of a coronary artery. Each year 
over 80,000 such operations are performed in the United States on 
patients with varying degrees of chronic disability from angina pectoris 
(chest pain). The precise indications and the long-term effects of the 
procedure still remain to be determined. While coronary artery surgery 
has received considerable acceptance in the United States, the method 
is much less extensively used in the U.S.S.R. Conversely, some medical 
approaches in the U.S.S.R. are unfamiliar or unknown to U.S. heart 
specialists and their coronary patients. 

During FY 1978, patient recruitment for the joint study continued 
in both countries. A U.S. delegation visited the Soviet Union in May 
1978, for a Joint U.S. -U.S.S.R. Working Meeting to discuss the ongoing 
U.S. -U.S.S.R. study of the management of ischemic heart disease, and 
to discuss plans for future collaborative research and activities. The data 
from the U.S.S.R. come from patients at the Myasnikov Institute and 
are part of the ongoing Soviet studies. The patients from the U.S. side 
come from a national trial involving 15 centers comparing the medical 
and surgical management of ischemic heart disease. During the meeting, 
the U.S. and U.S.S.R. scientists agreed that the cooperative study had 
reached the stage where the data from the two arms of the study should 
be computerized and put in a form facilitating regular interchanges of 
information for data analysis. This computerization of joint clinical 
data is currently in progress at the U.S. Coordinating Center in Seattle. 
The variables include: detailed coronary angiography, ventriculography, 
exercise testing with electrocardiography, detailed history, and labora- 
tory data. All of these examinations are carried out according to stan- 
dardized joint protocols. 

During FY 1978, the Proceedings of the First U.S.-U.S.S.R. Joint 
Symposium on the Management of Ischemic Heart Disease (18 papers) 
held in Moscow, October 1976, were published in English and will be 
published in Russian in the Soviet Union in the near future. 

Myocardial Metabolism. Myocardial metabolism, or area 3, in- 
volves joint basic studies of activities and functions of healthy and 



68 



diseased hearts, a subject relating to many areas of cardiovascular re- 
search. A fundamental understanding of the structure and function of 
the heart muscle is crucial to the development of improved methods of 
prevention and therapy. Specifically, it is important to search for thera- 
pies which will enable the heart muscle to survive a heart attack and to 
develop methods to prevent additional heart muscle damage. The joint 
U.S.-U.S.S.R. collaboration has emphasized these areas. 

The collaboration in area 3 has focused on joint symposia, ex- 
changes of senior scientists, joint laboratory studies by junior scientists 
for extended periods of time, and a series of joint publications. Three 
Joint Symposia on Myocardial Metabolism have been held since the 
beginning of this exchange in 1972. Altogether, 76 scientific reports 
were presented. The proceedings of all three symposia have been pub- 
lished in English and in Russian, the latest one in FY 1978. Hundreds of 
scientists and physicians have participated in the exchange during the 
symposia and visits to laboratories, clinics, and scientific institutions in 
both countries. 

During FY 1978 three senior U.S. scientists and two U.S. fellows 
visited U.S.S.R. research institutes to engage in joint activities in myo- 
cardial metabolism. The U.S.S.R. coordinator for area 3 visited the 
United States in May 1978, to discuss further plans. A U.S. planning 
meeting was held in April 1978. Both sides agreed on the following 
topics for the Fourth U.S.-U.S.S.R. Joint Symposium to be held in the 
U.S.S.R. in September 1979: hormone action, calcium and membranes, 
amino acid metabolism, energy metabolism, and myocardial ischemia. 

The collaborative efforts have greatly expanded the exchange of 
information on myocardial metabolism. Each side has agreed to continue 
joint laboratory investigations in five areas of basic research. Joint 
presentations of the results of the U.S.-U.S.S.R. studies to date have 
been made at scientific meetings in the United States and Europe, and 
a number of joint papers have been published. The potential benefits 
of this collaboration may be considerable in terms of identifying new 
approaches to the treatment and prevention of heart disease. This pro- 
gram has already had an impact on the direction of research in both 
countries, particularly in the area of protecting the heart muscle follow- 
ing a heart attack. 

Congenital Heart Disease. Congenital heart disease is a serious 
illness among children of both countries. It can cause premature death 
or impair the quality of life from childhood to adulthood. 

The objectives of the U.S.-U.S.S.R. collaboration in this area are 
to explore new methods of diagnosis and postoperative care in order to 
further reduce mortality from congenital heart disease and improve the 
surgical treatment of complex heart defects, particularly in very young 
infants. Each year about 25,000 children in the United States are born 
with defective hearts. Of the 6,500 of these children who die annually, 
approximately half are less than 1 year old. Collaborative activities have 
focused on joint symposia, joint working meetings, and exchange of 
senior specialists and fellows. Three joint symposia have been held. 



69 



Seventy-three reports presented at these symposia have been published 
in English and in Russian. The Proceedings of the Third Joint U.S.- 
U.S.S.R. Symposium on Congenital Heart Disease, Bethesda, April 
14-15. 1977, were published in FY 1978. 

A U.S. cardiovascular surgeon visited the Soviet Union during 
FY 1978 to exchange information with U.S.S.R. surgeons concerning 
congenital heart disease, to present lectures on topics of current joint 
interest, and to explore potential topics for the 1980 Fourth Joint 
Symposium on Congenital Heart Disease to be held in Moscow. 

The collaborative activities of U.S. and U.S.S.R, specialists have 
focused on the etiology and development of pulmonary hypertension; 
the natural history of ventricular septal defects; the mechanisms of 
blood coagulation in patients with circulatory hypoxia; and the theo- 
retical aspects and pathophysiology of extracorporeal circulation and 
deep hypothermia. The joint efforts have produced an expansion of the 
exchange of information related to the diagnosis, treatment, and follow- 
up care of patients with congenital heart disease. 

Sudden Death. Fifty percent of all deaths from coronary heart 
disease occur suddenly. The immediate mechanism of sudden death is 
believed to be a disturbance in the heart's rhythm. 

As a result of the joint cooperation in this area a working relation- 
ship has been developed between a group of U.S. and Soviet physician 
scientists. Advanced technology for monitoring of arrhythmias has been 
exchanged. U.S. scientists have collaborated with Soviet scientists in 
organizing a monitoring study for identifying subjects at high risk for 
sudden death in the Sokolniki area of Moscow. The Soviet side has 
shared data on coronary heart disease patients who underwent ambula- 
tory monitoring, and the United States has provided data on Multiple 
Risk Factor Intervention Trial subjects who have been screened for 
cardiac arrhythmias. 

The U.S.S.R. side has identified a large group of patients with 
complex arrhythmias who are at high risk of sudden death. This has led 
to a cooperative study in Moscow, using an acute antiarrhythmic drug 
testing protocol developed in the United States. During FY 1978 a U.S. 
exchange scientist spent 3 months in the U.S.S.R. cooperating in this 
study. The work dealt with an investigation of two new antiarrhythmic 
drugs: ethmozin, developed in the U.S.S.R., and a second agent, Mexile- 
tine. 

A Joint Symposium on Sudden Death was held in Yalta in Octo- 
ber 1977. The proceedings of the symposium were published In FY 1978 
in English and In Russian. Both sides have agreed to intensify the ex- 
change of information by preparing annotated bibliographies of the 
most Important recent papers on sudden death in their respective coun- 
tries and through the formation of U.S. and U.S.S.R. editorial groups to 
prepare articles for joint publication In U.S. and U.S.S.R. journals. As a 
result the exchange of information was Increased significantly during 
FY 1978. 



70 



Six areas have been designated for continued exchanges of special- 
ists. A U.S.S.R. working group will visit the United States in the fall of 
1978 to assist in planning the Joint Working Symposium on Sudden 
Death to be held in the United States in 1979. The delegation will also 
visit U.S. laboratories. 

The collaboration in area 5 should help bring into focus current 
activities and possible future discoveries concerning control of sudden 
death and the arrhythmias that may lead to sudden death. There is 
mutual recognition that effective control of sudden death will bring 
about significant reductions in coronary heart disease death rates in both 
countries. 

Blood Transfusion, Blood Components, and Prevention of Hepa- 
titis with Particular Reference to Cardiovascular Surgery. Blood re- 
sources, a nation's supply of blood and blood products, are critical to 
the health of its citizens. High quality blood management is a necessary 
adjunct to successful cardiovascular surgery as well as other forms of 
therapy. Prevention of hepatitis in transferring blood from donors to 
recipients is a goal common to both the United States and U.S.S.R. 

The past two decades have witnessed rapid advances in blood 
management. However, this progress has been matched by steady in- 
creases in demand caused by parallel advances in medical sciences and 
technology. This, in turn, necessitates continuous development of new 
approaches to upgrade blood therapy. 

The U.S. -U.S.S.R. cooperation has focused primarily on joint 
working meetings, exchanges of scientists for joint laboratory studies, 
and exchange of information at one symposium. Information has been 
exchanged on the U.S. blood transfusion system, blood service in the 
U.S.S.R., new methods of blood preservation used in the two countries, 
utilization of blood components, blood transfusion technology, problems 
of hepatitis, effects of massive blood transfusions, use of blood in cardi- 
ovascular surgery, and problems related to the use of blood in heart 
bypass systems. Collaborative activities focus on two areas: prevention 
of hepatitis in blood transfusion, particularly in cardiovascular surgery; 
and the use of whole blood, blood components and derivatives, emphasis 
on cardiovascular surgery. 

Joint studies on hepatitis were initiated in FY 1978. Altogether, 
about 1,000 serum samples from each country were exchanged. These 
cooperative investigations on the frequency of distribution of hepatitis B 
markers in sera of donors will provide information on the frequency and. 
etiology of post-transfusion hepatitis and particularly non-A, non-B 
hepatitis in cardiovascular surgery patients for clinical investigation of 
immune globulin of hepatitis B, and for the development and evaluation 
of vaccines against viral hepatitis B. 

Two U.S. fellows visited the U.S.S.R. during FY 1978 for joint 
laboratory studies and lectures on topics of joint interest in blood trans- 
fusion, blood resources, and hepatitis. The Soviet side shared informa- 
tion on a technique for significantly increasing the yield of antihemo- 
philic factor from blood. It is anticipated that application of this 



71 



technique in the United States will result in considerable savings in 
blood resources and costs. Two U.S.S.R. scientists visited the United 
States under the individual scientist exchange for discussions in area 6. 
A U.S. delegation visited the U.S.S.R. in September 1978, for a Joint 
U.S.-U.S.S.R. working meeting to present lectures, to develop further 
joint plans, and to visit U.S.S.R. laboratories collaborating in the ex- 
change. The Proceedings of the First U.S.-U.S.S.R. Symposium on 
Blood Transfusion were published during FY 1978. 

The investigations carried out in area 6 have emphasized the need 
to restrict the use of whole blood during cardiovascular surgery. There 
are now new possibilities to supplement whole blood with blood com- 
ponents and substitutes. It is hoped that the joint activities will lead to 
new approaches to blood transfusion methodology in cardiovascular 
surgery. 

Hypertension Etiology, Treatment and Prevention. Hypertension 
is one of the major health problems in the world, both in terms of its 
prevalence and its impact. About 35 million Americans (1 in 6) have 
definite high blood pressure (160/95 or higher) and are at significant 
risk for future cardiovascular, cerebrovascular, and renal disease. The 
prevalence of high blood pressure increases strikingly with age. It is 
twice as prevalent, and twice as malevolent in black Americans. Another 
25 million Americans have so-called "borderline" high blood pressure 
(with pressures between 140/90 and 160/95) and probably warrant regu- 
lar medical surveillance. The hypertension problem in the U.S.S.R. is 
also a serious one. As a result, the U.S.-U.S.S.R. joint committee de- 
cided to add Hypertension Etiology, Treatment, and Prevention as a new 
area of joint collaborative activities under the cardiovascular exchange in 
FY 1978. 

Two senior U.S.S.R. scientists visited the United States during 
FY 1978 to develop joint plans in this area, participate in meetings on 
hypertension, and visit scientific institutions and laboratories. A Joint 
U.S.-U.S.S.R. Symposium on Hypertension was held in June 1978 in 
Sochi. The aim of the symposium was to exchange scientific information 
on fundamental, clinical, and epidemiological aspects of hypertension in 
both countries. Both sides presented overviews of the hypertension 
studies in each country; approaches to methodology; experimental 
models of neural and humoral control of blood pressure; hemodynamic 
factors in hypertension; malignant forms of arterial hypertension; and 
epidemiology of hypertension. 

Interesting new hypertension findings from the Joint U.S.-U.S.S.R. 
Lipid Research Clinic Studies were reported. As a result of the use of 
common, highly standardized methods in epidemiological surveys carried 
out in the Joint U.S.-U.S.S.R. LRC program, it is possible to compare 
the prevalence and treatment status of high blood pressure in men 
sampled from Moscow, Leningrad, and nine U.S. communities. The 
preliminary data show that, in the populations studied, U.S.S.R. men 
aged 40-59 have higher levels of blood pressure than U.S. men of com- 
parable age. The prevalence of high blood pressure is two to three times 



72 



greater in Soviet than U.S. white men. Also, the prevalence of hyper- 
tension is higher in hyperllpidemic men than in random sample examin- 
ees in both countries. The U.S. delegation to the symposium also visited 
Soviet research institutes and work settings to discuss joint programs in 
hypertension. 

The Proceedings of the Joint l-iypertension Symposium will be 
published in English and in Russian. The following joint activities were 
agreed upon for the future: Cooperation in Basic and Clinical Research; 
Cooperation in Research on Hypertension Control; and a Second Joint 
Meeting on Hypertension in the U.S.A. in May 1979. 

Artificial Heart Researcfi and Development. In June 1974, after 
several years of exploratory discussions, both governments signed a 
3-year agreement designating the field of artificial heart research and 
development as a new area of cooperation. Mutual interest in this area 
stems from the recognition that present and foreseeable techniques of 
surgical and pharmacological management of acute and chronic heart 
failure and shock still leave a substantial fraction of patients with com- 
promised or fatally impaired heart function. By supportive mechanical 
devices, it is possible to assume some of the pumping function of the 
heart and to relieve its workload. Presently such techniques are appli- 
cable for brief periods in man and have been employed for longer 
periods in experimental animals. Studies of patients in the United 
States have shown a definite reduction in the workload of the heart 
following a heart attack when the heart is assisted during recovery by 
means of a mechanical pumping device. 

The U.S.-U.S.S.R. Agreement in Artificial Heart Research and 
Development was renewed in 1977 for a period of 5 years together with 
the overall health exchange agreement. The agreement calls for imple- 
mentation principally by exchange of scientific and technical informa- 
tion; organization of joint conferences; workshops and meetings of 
experts; exchange of specialists and delegations; preparation of joint 
publications and technical manuals; and familiarization with and ex- 
change of technical aids and equipment. 

In implementing the joint collaboration, an immediate problem 
was the disposition of rights on any patents resulting from collaborative 
work in this area of advanced technology. As a result of joint efforts, a 
bilateral agreement setting forth guidelines for disposition of intellectual 
property questions was signed by both sides in 1975 in Russian and in 
English. 

During the past several years the joint collaboration has empha- 
sized joint working meetings, exchanges of protocols, exchanges and 
testing of devices from each country, and exchanges of working teams 
and individual scientists. Six artificial hearts and one drive system from 
each side were exchanged during the first 3 years of the exchange. Prep- 
arations are in progress for the exchange of a vacuum forming device 
and biomaterials from the United States and a circulatory device control 
system from the Soviet Union. 



73 



During FY 1978 a delegation from the Soviet Union visited the 
United States for a joint U.S.-U.S.S.R. working meeting in Houston to 
discuss progress and to jointly draft plans for future activities. The dele- 
gation also visited a number of U.S. centers with ongoing research in 
circulatory device development. The agenda for the joint meeting in- 
cluded presentations on artificial hearts and several discussions of energy 
conversion systems for circulatory devices and circulatory device control 
systems. At the conclusion of the meeting, both sides agreed on contin- 
ued exchanges of scientists for work in each others' laboratories, ex- 
changes of individual scientists and delegations to further develop joint 
activities, and publication of joint articles on U.S.-U.S.S.R. activities 
and exchanges completed to date. The U.S. and U.S.S.R. scientists also 
agreed to hold a joint working meeting and a joint symposium in the 
U.S.S.R. in the fall of 1979 to review progress and to develop further 
plans. A joint publication on the exchange to date is in preparation. 

Two U.S.S.R. exchange fellows visited U.S. laboratories during 
FY 1978 for joint studies in artificial heart research and development; 
reciprocal exchanges of U.S. fellows are planned. 



Cooperation With Israel 

The Jerusalem Lipid Research Clinic is the latest addition to the 
NHLBI International Lipid Research Clinics Program. It was established 
by the Institute in 1975. During FY 1978 progress continued in the 
prevalence study of dyslipidemia and its natural history in the Jewish 
population of Jerusalem. The study screens 17-year-old boys and girls 
when they report for preinduction physicals for the Army. 

The attraction for performing this study in Jerusalem is the 
multiethnic character of the population. No other place in the world 
currently provides such an opportunity for conducting a multinational 
study in a microcosm. The ethnic groups represented in the study differ 
significantly with respect to heart disease rates, dietary patterns, educa- 
tion, and socioeconomic status. The current study will be completed in 
1979, with an additional 2 years required for followup analysis of the 
data. The target is to screen about 15,000 individuals by the end of 
1979, approximately 7,500 youngsters and 7,500 adults. About 8,000 
youngsters and 5,300 adults had been screened as of July 1978. 

While the study is still ongoing, sufficient numbers of individuals 
have been screened to allow preliminary analyses of the data. Important 
findings already have been noted on differences in lipid distribution in 
the population, dietary differences in fat intake, and comparative data 
on the national diets of the United States and Israel. 

The results of international investigations such as those conducted 
in the U.S. and Jerusalem LRC's are of great importance to medical 
science. If these studies establish that lowering blood cholesterol indeed 
decreases the risk of heart attacks, many lives will be saved. However, if 
the studies determine that lowering cholesterol does not prevent heart 



74 



attacks, our society can be spared the expense and social hardship of 
cholesterol-lowering diets and drugs. In either case, the medical infor- 
mation originating from the LRC international investigations will pro- 
foundly affect millions of lives in this and future generations. 



Cooperation With the Federal Republic of Germany 

During FY 1978 the Institute continued its cooperation with 
scientists in the Federal Republic of Germany (F.R.G.) under the Agree- 
ment on Cooperation in the Fields of Biomedical Research and Tech- 
nology signed in September 1976 by the U.S. Assistant Secretary for 
Health and the Minister of Research of the F.R.G. 

The German side expressed a special interest in collaboration in 
cardiovascular disease, and a series of planning meetings were held dur- 
ing FY 1978 to develop plans for joint activities in this area. As a 
result, collaborative activities were initiated in two areas, arteriosclerosis 
and hypertension. Projects to be considered will fall within the spectrum 
of etiology, pathogenesis, and prevention. Both sides exchanged exten- 
sive information on ongoing projects in arteriosclerosis and hypertension, 
and the German side developed proposals for potential joint collabor- 
ation. In many cases collaborative activities were already under way 
with U.S. laboratories. Some of the proposals dealt with the need for 
developing standardized assays for biologically active compounds such 
as the reninangiotensin system and plasma lipoproteins and apoproteins. 
It was felt that development of such common methodologies and their 
adoption in the United States and F.R.G. would allow accurate compar- 
isons of data by different laboratories and would allow the development 
of a more comprehensive data base than would otherwise be possible. 
Since the German data base is tied to the rest of Europe, adoption of 
such methodologies would make it possible to obtain comparative epi- 
demiological data not only for the U.S. and Germany but also for 
other countries in Europe. 

A Joint U.S. -F.R.G. VVorkshop on Hypertension and Arterioscler- 
osis was held in Heidelberg in August 1978 to review the proposals for 
potential joint activities and to develop plans for joint or comple- 
mentary activities. The emphasis was on linking ongoing projects in 
both countries and on the exchange of scientists. 

At the conclusion of the workshop, a Joint Summary of Dis- 
cussion was signed by both sides outlining plans for further activities. 
It was agreed that the U.S. -F.R.G. agreement provided an important 
opportunity for advances in biorfiedical research and health care which 
might benefit the peoples of both countries. The proposals developed 
by the German side were most valuable in the discussions. The two sides 
agreed that the proposed U.S. -F.R.G. activities in prevention, education, 
and control will necessitate continued basic biomedical research in both 
countries. Highest priority was given to the exchange of biomedical 
scientists. Priority was recommended in establishing German studies 



75 



(data sites) on cardiovascular disease, morbidity and mortality, and risk 
factors similar to those developed from studies in the United States. 
The German side expressed an interest in having U.S. scientists work 
with them in the planning and development of such studies. Also, the 
German side accepted the U.S. invitation for an F.R.G. delegation to 
attend the National Heart, Lung, and Blood Institute Conference on the 
Decline in Coronary Heart Disease Mortality to be held in Bethesda in 
October 1978. 

The U.S. delegation's itinerary included visits to laboratories and 
clinics. In addition, the NHLBI Director was invited to Bonn to meet 
with representatives of the three ministries participating in the U.S.- 
F.R.G. exchange in the cardiovascular area. The purpose of these meet- 
ings was to discuss policy and administrative questions concerning 
future cardiovascular exchanges. The German side is particularly inter- 
ested in duplicating the U.S. experience in the decline of cardiovascular 
disease. The Institute is looking forward to collaborating with the F.R.G. 
side to further delineate the role of various risk factors thought to be 
responsible for the positive change in cardiovascular disease in our own 
country. The two sides have agreed to develop a data base of ongoing 
investigations, especially as they relate to programs of intervention on 
risk factors. A meeting of scientists from both countries will be held in 
the second part of 1979 to share data and to develop specific plans for 
joint studies. 



Cooperation With the Republic of Italy 

During FY 1978 the Institute initiated collaboration with Italy 
under the Memorandum of Understanding between the Department of 
Health, Education, and Welfare of the U.S. and the Ministry of Health 
Health of the Italian Republic for Cooperation in the Field of Health 
and Medicine, signed in November 1977. A series of joint planning 
meetings were held in accordance with a joint implementation plan 
agreed upon in March 1978 for collaboration in the prevention of heart 
disease. The plan calls for three types of initial activities: exchange of 
information on pertinent U.S. and Italian studies; translation of key U.S. 
and Italian documents into Italian and English, respectively; and a Joint 
U.S. -Italian Workshop on Measurement and Control of Cardiovascular 
Risk Factors and visits to Italian scientific institutions and laboratories. 
The purpose of the workshop, held in December 1978 in Rome, will be 
to exchange, review, evaluate, and compare U.S. and Italian information 
on mortality, morbidity, prevalence, and incidence data on cardiovascu- 
lar diseases; nutritional data; relationships and trends between major risk 
factors and cardiovascular disease; and methodologies for measurement 
and control of risk factors. Three cardiovascular risk factors will be high- 
lighted: hyperlipidemia-nutrition, hypertension, and smoking. 



76 



Cooperation With Poland 

The Minister of Health for Poland and a delegation of health 
experts visited the NHLBI in September 1977 to discuss opportunities 
for joint collaboration in heart and vascular diseases, lung diseases, blood 
diseases, and blood resources. The Minister extended an invitation to the 
Director, NHLBI, to visit Polish research institutes in the spring of 1978. 
The visit has been postponed and will be rescheduled in the future. 

A Joint U.S. -Polish Symposium on Cardiovascular Diseases will be 
held in Bethesda in November 1978 at the request of the Polish Ministry 
of Health in recognition of U.S.-Polish "Medical Week." The meeting 
will deal with epidemiology of cardiovascular diseases, overview of major 
areas of research emphasis, specific discussions of research in hyper- 
tension and arteriosclerosis, the transfer of technology in cardiovascular 
diseases, and cardiological care and postgraduate education. 

As part of the ongoing U.S. -Poland cooperation in biomedical 
research which provides counterpart P.L. 480 currencies, progress con- 
tinued on the Research Agreement for the Polish component of the 
ongoing European Collaborative Trial in Multifactorial Prevention of 
Coronary Heart Disease, signed in November 1976. During FY 1978, 
Institute staff visited Poland to review and discuss the data with their 
Polish colleagues. In both Warsaw and Cracow factories participating in 
the trial, cooperation in the screening program was excellent with an 
average participation in all factories of about 88 percent. Nearly 9,000 
screening examinations were completed (the goal is 10,000), 8,042 in 
factories designated as "intervention" factories and 713 (a targeted 10 
percent of the factory employees) in the "control" factories. Risk 
factors targeted for intervention include hypercholesterolemia, over- 
weight, hypertension, smoking, and lack of physical activity. Preliminary 
data show blood pressure and cholesterol values to be higher in Warsaw 
than in Crakow. Prevalence of cigarette smoking is much higher than in 
the U.S. study: 62 percent current smokers (Warsaw) vs. 37 percent 
(U.S.). 



Cooperation With Yugoslavia 

An agreement between the Government of the United States and 
the Government of Yugoslavia was signed in May 1973 to encourage 
research between the two countries on projects of mutual interest. With 
the P.L. 480 funds provided under this agreement, NHLBI scientists 
have collaborated with Yugoslav scientists on two projects, one dealing 
with Epidemiology of Cardiovascular Diseases, and the second with Epi- 
demiology of Respiratory Diseases. This international collaboration has 
yielded a number of interesting new findings and gained the attention of 
the international medical community. Joint review and analysis of the 
data continued in FY 1978. 



77 



More than 11,000 Yugoslav men are included in the long-range 
followup for cardiovascular risk factors. The coronary heart disease 
(CHD) incidence in Yugoslav men appears to be extraordinarily low. It 
is about one-fourth the incidence in the U.S. Framingham study. By 
comparison, the CHD incidence among men in the Framingham study is 
typical of that found in a number of comparable prospective studies in 
the United States. The Framingham incidence, in turn, is double that in 
Puerto Rican men and Japanese men living in Honolulu. Some of the 
results of the U.S.-Yugoslav collaborative study will be reported at the 
October 1978 International Symposium on Essential Hypertension to be 
held in Yugoslavia at the initiative of the principal investigator on the 
U.S. -Yugoslavian project. Repeat measurements of blood pressures taken 
7 years apart show increases in both diastolic and systolic pressures and 
increases in the prevalence of high blood pressure over this period. The 
increases are larger in rural than in urban areas. It will be of interest to 
see whether these trends will continue as the impact of Westernization 
continues. 

During FY 1978, work also continued on the analysis of data from 
the large respiratory project conducted in Yugoslavia with P.L. 480 
funds in which about 3,000 individuals have been phenotyped for anti- 
trypsin genes. The basis for this extensive study is the finding that a 
genetic defect resulting in a deficiency of the enzyme alpha-1-anti- 
trypsin has been identified as a factor in the development of a severe 
form of familial emphysema which attacks young adults. Unexpectedly, 
during this study, a new antitrypsin gene was discovered and first identi- 
fied in Belgrade and St. Louis with subsequent verification by other 
laboratories. This study was completed in FY 1978 but analysis and 
publication of results is likely to continue in the future. 



Cooperation With Great Britain 

Scientists from the NHLBI Division of Intramural Research con- 
tihued their cooperation with scientists from Great Britain in the devel- 
opment of a computer-based chemical information system (CIS). While 
the management for the CIS continued to be located in NHLBI, funding 
during FY 1978 was largely drawn from the NIH management fund. 
During FY 1978 the development of the CIS progressed faster than at 
any time in the past. The system includes analytical programs to accom- 
plish iterative analysis of complex NMR spectra, or general curve fitting 
and linear regression analysis. The data base for the system was as- 
sembled by the joint efforts of the National Institutes of Health, the 
Mass Spectrometry Data Center (within the Department of Industry of 
the British Government), and the Environmental Protection Agency, 
with participation from several other U.S. Government agencies as well 
as nongovernment U.S. units. This valuable information system is being 
made available to scientists in North America and in Europe by means 
of an international teleprocessing network. 



78 



The following countries currently cooperate in the further develop- 
ment of CIS: Finland, France, Germany, Holland, Hungary, Japan, 
Poland, Sweden, Switzerland, U.S.S.R., and Yugoslavia. 



Cooperation With Other Countries 

The National Heart, Lung, and Blood Institute participates in the 
work of the NIH Coordinating Group for the U.S.-Egyptian Joint Sub- 
committee on Biomedical Research. The Egyptian side has submitted 
proposals in several areas falling within the Institute's mission and an 
Egyptian scientist visited the U.S. in FY 1978 to develop a joint re- 
search proposal. The Institute continued informal contacts with Japan 
in the cardiovascular, lung, and blood resources areas. The director. 
Division of Lung Diseases, NHLBI, is the NIH representative on the 
Panel on Lung Physiology and Technology of the U.S. -Japan Natural 
Resources Agreement. NHLBI staff members were invited to Japan in 
the fall of 1978 to participate in joint meetings on hypertension and 
meetings of the U.S. -Japanese Panel on Malnutrition. The Institute has 
indicated interest in participating in the proposed U.S. -Japan umbrella 
agreement. The NHLBI continued to assist in the analysis of the British- 
Norwegian Migrant Study. The Institute also collaborates in the U.S.- 
France Agreement for Scientific and Technological Cooperation in 
research on lung diseases. Proposals are pending for Institute participa- 
tion in collaborative activities with several additional countries. 



Coordination With international Organizations 

During FY 1978 the Institute continued to collaborate with the 
WHO. The Director, NHLBI, was appointed advisor to WHO in long- 
range planning of programs in cardiovascular diseases. Institute staff 
collaborated with the International Society and Federation of Cardi- 
ology and WHO in developing programs for World Health Day, April 7, 
1978, which was devoted to hypertension. NHLBI staff participated in 
WHO planning workshops on: hypertension; links between cardiovascu- 
lar diseases and other chronic diseases; long-term effects of coronary 
bypass surgery; and the WHO Cooperative Study of Present Research on 
Atherosclerosis and Hypertension Precursors in the World. The Institute 
also continued to contribute to the WHO Mild Hypertension Liaison 
Committee. 



International Visitors and Meetings 

During FY 1978 the Institute received many international scien- 
tists for joint work in the laboratories of the Division of Intramural 



79 



Research, NHLBI. These scientists came from Australia, Brazil, Came- 
roun, Canada, Great Britain, India, Israel, Italy, Japan, Mexico, Peru, 
South Africa, and Taiwan. Many international scientists participated in 
the Fourth U.S. National Conference on High Blood Pressure Control. 

The Institute staff attended a number of international scientific 
meetings during FY 1978, actively participating in these meetings as 
speakers, panelists, and chairmen. Examples of important meetings are: 
World Conference of International Union Against Tuberculosis and 
Respiratory Diseases; World Congress of Cardiology; International Sym- 
posium on Diet and Atherosclerosis in Pediatrics; International Congress 
of Pediatrics; Latin American Congress of Pathology; International 
Society of Hypertension; International Congress of Nephrology; Inter- 
national Congress of Pharmacology; International Biophysics Congress; 
Congress of the International Academy of Pathology; International 
Symposium on Prophylactic Approach to Hypertensive Disease; and the 
International Society of Hematology and International Society of Blood 
Transfusion meetings. 

An Institute staff member visited Africa at the invitation of the 
College of Medicine in Nairobi, Kenya, and brought back reports on the 
many illnesses and deaths preventable in terms of U.S. medical practices. 



Institute Trends in International Activities 
and Proposed New Directions 

International cooperation in health is in the interest of the citizens 
of the United States as well as those of other countries. It provides an 
important and unique resource for expanding and sharing America's own 
resources for dealing with problems in health research and health care. 
Through such cooperation the talents, insights, and experiences of many 
nations can be brought to bear on the analysis and planning of U.S. 
national programs as well as priority setting for the future. By making 
fuller use of the international resources in science and medicine, the 
Institute hopes to create an even stronger base for the future develop- 
ment of the National Heart, Blood Vessel, Lung, and Blood Program 
mandated by the President and the Congress and thereby improve and 
cut the costs of health care for U.S. citizens. 

In recent years, the United States has increasingly encouraged 
international cooperation in biomedical research by entering into bilater- 
al health exchange agreements and by authorizing the expenditure of 
funds for international activities. In a statement emphasizing the impor- 
tance of "International Health Programs" the President's Biomedical Re- 
search Panel stated, "There is now a steadily growing, international 
community of biomedical science in which the free exchange and the 
setting up of collaborative scientific projects represent not only practical 
steps toward more productive research but also perhaps, an encouraging 
manifestation of the comity of nations." 



80 



By bringing the total international experience in biomedical 
research to bear on specific national progranns and by developing joint 
programs with other nations in selected areas of mutual interest it 
should become possible for the United States as well as other countries 
to realize significant savings in cost, resources, and time to bring about 
mutually desirable health outcomes. For instance, the development of 
standardized international methodologies will help decrease the need for 
duplicating large-scale studies done in other countries. 

Since the passage of the National Heart, Blood Vessel, Lung, and 
Blood Act in 1972, the international activities of the National Heart, 
Lung, and Blood Institute have expanded significantly reflecting the 
increasing encouragement by the Department of Health, Education, and 
Welfare and the Department of State to expand international coopera- 
tion in biomedical research. There has also been a parallel increased 
interest on the part of foreign governments to establish formal interna- 
tional agreements for collaborative programs in the areas falling within 
the mission of the national program. 

The world problems in cardiovascular, lung, and blood diseases and 
blood resources are interrelated, and it is important that a global per- 
spective be sought in constructing means for finding solutions to these 
problems. Nationally and internationally there is a new preoccupation 
with the interrelationships between economic considerations, health 
status, and health outcomes. Comparisons are being made between the 
costs and resources required to bring about various levels of improve- 
ment in health status by different means, whether scientific, economic, 
or social in nature and between various systems of delivery for these 
improvements, and the Institute is aware of these concerns. 

Unless preventive measures are taken, past experience in the 
industrialized nations strongly indicates that the socioeconomic advances 
desired by developing nations as well as developing segments of our own 
society will be accompanied by a costly epidemic rise in cardiovascular 
and other diseases similar to that now experienced by most industrial- 
ized nations. This can be prevented by international collaboration and 
sharing of knowledge and experiences in health research. 

A number of specific opportunities for continuing and new inter- 
national collaborative efforts were identified during FY 1978. These will 
be pursued in accordance with national priorities and as resources be- 
come available for international activities. It is planned that these pro- 
grams be developed in an orderly manner (i) by following through on 
specific leads identified by U.S. scientists, (ii) by following up on indi- 
cations of interest from scientists and government officials from other 
nations with respect to unique patient populations or unique resources 
that could be explored jointly with U.S. investigators, and (iii) by 
exchange visits and joint programs in areas of common need and mutual 
interest. 

Specifically, the Institute plans to continue ongoing bilateral 
exchange programs and collaboration with the World Health Organiza- 



81 



tion in the planning and development of long-range international pro- 
grams in cardiovascular disease. Plans are in progress for a joint U.S.- 
P.R.C. scientific meeting on "Cardiovascular Diseases" to be held in 
November 1978, at the National Heart, Lung, and Blood Institute at 
the request of a delegation of cardiologists from the People's Republic 
of China. A Joint U.S. -Polish Symposium on "Cardiovascular Diseases" 
is also scheduled for November 1978, at the request of the Polish Min- 
istry of Health in recognition of U.S. -Polish Medical Week. During 
FY 1978, the Institute also had a number of visits from representatives 
of Eastern European countries interested in collaboration and we expect 
these contacts and exchanges to continue in the future. 

The HEW trend during the past year has been to focus attention 
on the increasing need for industrialized nations such as the United 
States to help countries which are less economically advantaged in their 
health research development. Some of the inquiries received have been 
close to home as exemplified by the efforts to focus attention on 
research programs along the U.S. -Mexico border. Others have dealt with 
developing countries in Asia, Africa and Latin America. The Institute is 
interested in cooperating in these efforts by the U.S. Government to 
share experience and develop joint research with developing countries. 
Specific opportunities for collaboration have been identified. The extent 
to which the Institute can implement these plans will depend upon the 
availability of U.S. funds for travel and program operation of such 
activities. 

The National Heart, Lung, and Blood Institute plans to continue 
to develop its international role within the policies and budgetary con- 
straints set by the President and the Congress. We expect this develop- 
ment to include formal as well as informal arrangements in accordance 
with national priorities and new international leads and opportunities 
for scientific exchange. 



National Institute on Aging 



The broad mandate of the National Institute on Aging (NIA) for 
a multidisciplinary approach to the study of aging is reflected in the 
Institute's international activities. Foreign visitors to NIA represent a 
variety of disciplines and interests. NIA cooperated with the Swedish 
Embassy in planning miniconferences in six cities whereby Swedish 
gerontologists discussed their programs and activities in aging. A con- 
ference on senile dementia brought together American and foreign ex- 
perts to discuss and exchange information on the study of this problem. 

In the Spring of 1978, Dr. Milo D. Leavitt, former Director of 
Fogarty International Center and currently the NIA Director's special 



82 



assistant for Medical Program Development and Evaluation, spent 6 
weeks visiting 8 of the 10 British medical schools with chairs in geri- 
atric medicine and studying the educational, research, and service aspects 
of geriatric medicine in that country. His purpose was to determine 
training opportunities that might be developed via a fellowship program 
in geriatric medicine for postdoctoral U.S. physicians. 

The NIA nominated Sir Ferguson Anderson, a well-known British 
geriatrician, to be a Fogarty International Scholar. He plans to arrive in 
September 1979, to participate in activities to further the development 
of geriatric training in the United States. 

P.L. 93-296, The Research on Aging Act of 1974,created the NIA 
to promote research into the biological, medical, psychological, social, 
and behavioral aspects of aging. 

Aging research spans a wide range of disciplines from cellular 
biology to the social sciences, i.e., studies of the aging processes, social 
and psychological factors associated with aging, and alleviation of prob- 
lems of old age. Such studies are conducted at NIA's laboratories and at 
other research institutions through grants from NIA. 

The mission of NIA is to study the aging process and factors 
associated with aging, and the alleviation of problems of aging. This 
mission differs from those of Institutes charged with research related to 
specific diseases. The NIA, therefore, cooperates with other Institutes in 
studies of diseases associated with aging. With the growing aged popula- 
tion in the United States and in the world, all nations are aware of the 
need for research in aging. 

In cooperation with FIC and WHO, NIA, in November 1977, con- 
vened the directors of national institutes in other countries with pro- 
grams in the field of aging to discuss geriatric teaching, training, research, 
and services in their countries. A followup conference of these directors 
was held in Toyko, Japan, August 1978, in connection with the Inter- 
national Congress of Gerontology. 

A roundtable discussion was held with the U.S. Senate Special 
Committee on Aging and with Mrs. Carter at the White House during 
the November 1977 conference. 

In November 1978, a delegation from the Ministry of Health, 
Budapest, Hungary, met with staff to explore research opportunities of 
mutual interest and the possibility of future collaboration between the 
United States and Hungary. 

Both WHO and the U.N. are addressing the problems of the aged. 
The U.N. has passed a resolution for a World Assembly on Aging in 
1982 at which NIA expects to play a major role. In addition to such 
conferences, the exchange of scholars and information is vital to the 
dissemination of knowledge. 

NIA will continue to provide assistance and information and play 
a consultative role in research on aging, particularly to developing 
nations. 



83 



National Institute of Allergy and Infectious Diseases 



Introduction 

Since health problems of the tropjcal and developing countries 
are still largely those of infectious diseases, much of the biomedical 
r&search supported by the National Institute of Allergy and Infectious 
Diseases (NIAID) has strong international application. In addition to the 
usual tropical and parasitic diseases that commonly come to mind, such 
as malaria, schistosomiasis, cholera, and leprosy, the developing world is 
also plagued by diseases much more familiar to us in the temperate 
world such as hepatitis, the virus respiratory and enteric diseases, sexual- 
ly transmitted diseases, tuberculosis, and various allergies. The infectious 
diseases are often more prevalent and more severe in the tropics and 
developing countries as a result of poor sanitation, inadequate education 
about how diseases are spread and prevented, and the common occur- 
rence of malnutrition, all factors which combine to intensify the impact 
of these problems. The objectives of NIAID-supported research activities 
of international interest are the same as those for its domestic interests, 
namely, to supply new information on disease mechanisms that is 
requested to develop improved methods for diagnosis, treatment, and 
prevention. 

The work of NIAID takes place in laboratories at the NIH as well 
as in those at academic institutions in the United States supported by 
grants or contracts from the NIAID. A few grants are made to investi- 
gators in foreign institutions, but these must compete for funding suc- 
cessfully with the large number of high quality domestic research grant 
applications. Several other mechanisms are available for support of 
research in tropical medicine: grants to U.S. institutions with a close 
link to a foreign institution (ICMR Program), and collaborative research 
funded in certain countries with U.S. -owned foreign currency (P.L. 480). 
Additionally, there are bilateral medical science research programs with 
several countries, such as the U.S. -Japan Cooperative Medical Science 
Program. Table 1 lists the main categories of NIAID programs In tropical 
medicine and their approximate budgets In FY 1978. 

While much of the research on Infectious and allergic diseases 
supported by NIAID Is generally applicable to those same categories of 
disease throughout the world, the remainder of this report will empha- 
size primarily the research work supported by the NIAID that relates to 
those special health problems of the tropical and developing countries 
which have minimal direct Impact In the United States. 



Extramural Program of Grants and Contracts 

Of the total portfolio of NIAID extramural grants and contracts, 
212 could be considered in the areas of tropical medicine since they 



84 



Tai3le 1. Main Categories of NIAID Programs in 
Tropical Medicine and International Health — FY 1978 



Extramural Program* 

(Parasitology, medical entomology, 
leprosy, cholera, arbovirology) 

Grants and Contracts $14,633,951 (212) 

Intramural Program 

LPD (59 personnel) $3,158,000 

RML 1/10 (13 personnel) 402,000 

Total Tropical Medicine $18,193,951 

Foreign Competing Grants $ 810,452 (26) 



Total International $19,004,403 

*The U.S.-Japan Program grants and contracts are included but this does not 
include the ICMR's. 

dealt with research in parasitology, medical entomology, cholera, and 
arbovirology. In addition, 26 competing grants were made to investiga- 
tors in foreign countries, but only 2 or 3 of these were in the field of 
tropical medicine or parasitology. These 212 domestic and 26 foreign 
grants or contracts include grants and contracts for the U.S.-Japan Pro- 
gram, but not for the International Centers for Medical Research 
(ICMR's); however, these programs are described separately. The legisla- 
tive authority for NIAID grants and contracts stems from the Public 
Health Service Act of 1955, Public Law 81-692, Title III, Part A, 
Section 301, and Title IV, Part D, Section 431. 

The objectives of the program are the development of new knowl- 
edge applicable to diagnosis, prevention, and treatment of the relevant 
tropical and parasitic diseases. 

During FY 1978, total expenditures for the NIAID Tropical Medi- 
cine Extramural Program of 212 grants referred to above was nearly 
$14 million. This could be broken down to 148 grants for about $9.5 
million in parasitology and medical entomology, 15 grants of $1.4 
million for work on leprosy and cholera, and 19 grants in arbovirology 
for $1.9 million dollars. Another $1 million is allotted to 20 fellowship 
and training grants. These data are tabulated in table 2. 



85 



Table 2. NIAID-EP Tropical Medicine Program - FY 1978 



212 Grants 



10 Contracts 



— Parasitology and Medical Entomology 

Research 
Training 
Fellowships 
Research careers 



Subtotal 



— Leprosy 

— Cholera 

— Arbovirology 



Total 



$ 9,578,770 (148) 

562,393 ( 9) 

167,816 ( 13) 

272,798 ( 8) 

$10,581,957 (178) 

$ 577,025 ( 6) 

$ 830,948 ( 9) 

$ 1,900,309 ( 19) 

$13,890,239 (212) 



Does not include 4 ICMR's for $2,100,000 (est.) 



— (U.S. -Japan Progrann only) 

— Schistosomiasis 

— Filariasis 

— Leprosy 

— Cholera 

— Arbovirology 



$ 


118,080 ( 


: 1) 


$ 


136,454 ( 


: 3) 


$ 


230,485 ( 


; 3) 


$ 


258,693 ( 


: 3) 


$ 


( 


; 0) 


$ 


743,712 ( 


: 10) 



Sonne of the research findings reported during FY 1978 from the 
Extramural Program are summarized below. For purposes of brevity 
they cover only the diseases given emphasis by the WHO/TDR program 
on international health, including leprosy. 



Malaria 

The NIAID supports 12 individual research grants involving ma- 
laria. One of the grantees has successfully separated sporozoites of 
several Plasmodium species from mosquito debris and microbial contents 
by passing mosquito material through a DEAE-cellulose column. This 
simple technique has made possible not only the elimination of most of 
the contaminants, but the recovery of large numbers of viable sporozo- 
ites that have retained their infectivity, immunogenicity, and capacity to 
react with known antisera. This technique will be utilized in a long-range 
study of active and passive immunity against malaria. Another grantee 
has been able to develop a simple, effective means for differentiating 
parasite and host cell membranes by staining with cationized ferritin 



86 



followed by electron microscopic observation. He showed that the sur- 
face membranes of the parasite differ from one another and from the 
plasma membrane of the erythrocyte. Employment of these techniques 
should enable investigators to assess the purity of isolated parasite prepa- 
rations as well as aiding in identification of various membrane systems 
found in the parasite after subcellular fractionation. 



Schistosomiasis 

The NIAID supports 25 individual research grants relating to schis- 
tosomiasis, as well as 2 fellowships, 3 training grants, and 1 program 
project. A contract to supply investigators with mammals of vectors 
infected with several strains of the three human species of schistosomes 
has continued to stimulate research on a broad scale. 

In a grant-supported field study of a population in an endemic 
area of schistosomiasis in the Philippines, several commonly used diag- 
nostic tests were compared. This study showed that the filter paper 
circumoral precipitin test is neither reliable nor sensitive despite its 
popularity and mass application. Another grantee has isolated a potent 
inhibitor of activated Hageman factor in S. mansoni. This inhibitor may 
explain the ability of adult worms to avoid contact activation of the 
coagulation system in situ in the mesenteric veins. In a study of snail- 
trematode interactions, with the ultimate goal of finding clues leading to 
the development of schistosome biocontrol, a third grantee has shown 
that natural resistance in snails may be highly specific, involving not 
only distinct species but parasite strain differences as well. 



Filariasls 

The NIAID supports 10 individual research grants relating to filari- 
asls. The Institute also funds a supply contract to provide investigators 
throughout the United States with animals and vectors infected with 
various species of filarids. This contract, as in the case of the schistoso- 
miasis supply contract, supplies researchers who would otherwise be 
unable to obtain or maintain parasite life cycles but whose disciplines 
(immunology, pharmacology, biochemistry, etc.) must be brought to 
bear on the complex problems involved in the overall control of these 
tropical diseases. Two smaller contracts have as their objective the 
development of techniques for the cryopreservation of filarid material. 
Such techniques are essential in the shipment of samples of human 
filarial parasites from field collection sites to base laboratories, particu- 
larly those in the United States. 

One NIAID grantee has shown that in the cat model of elephanti- 
asis a concurrent infection with beta hemolytic streptococci results in 
greatly increased pathology. This is the first experimental study carried 
out in an animal model resembling human elephantiasis. 



87 



Another grantee has demonstrated that a snriall particle size formu- 
lation of a new antifilarial drug (CGP4540) has a high chemotherapeutic 
activity when administered in a single oral dose to gerbils infected with 
the filarial worm, Brugia pahangi. This formulation has also been found 
to be highly effective against schistosomes. To date no toxic effects have 
been noted. 



Trypanosomiasis 

Individual NIAID research grants relating to trypanosomiasis have 
been made to 13 investigators. In addition, the Institute supports one 
training grant. Research under these grants is concerned with trypano- 
some pathogenicity, metabolism, chemotherapy, and immunology. In a 
comparative study of the antigenic differences between pathogenic and 
nonpathogenic trypanosomes, one of the grantees has shown that the 
reproduction-inhibiting antibody, albastin, produced by the nonpatho- 
genic T. lewis/ "s an avid IgG antibody. The relevance of this finding is 
that it is now technically possible to isolate, purify, and characterize its 
antigen. Such knowledge should provide insight into how parasite repro- 
duction is controlled by the host. 

A second grantee is growing the causative agent of African trypan- 
somiasis in vitro. Growing T. rhodesiense in vitro in hamster lung is 
making possible long, in-depth, sophisticated biochemical studies. The 
parasites have been maintained for over 3 months with retention of 



infectivity to rats and mice. 



Leishmaniasis 

The NIAID supports 6 individual research grants on leishmaniasis. 
One of these grantees, located at the World Health Organization, has 
been studying normal mouse peritoneal macrophages that have been 
infected in vivo with Leishmania enriettii. When infected macrophages 
were exposed to activating stimuli, the parasites were rapidly killed and 
digested. Activation of macrophages was obtained by incubation of 
syngeneic lymphocytes stimulated in mixed cultures containing con- 
canavalin A and endotoxin. 

Another NIAID grantee has isolated RNA from highly purified 
kinetoplast mitochondrial fractions of Leishmania tarentolae and has 
demonstrated that in vivo transcription of 9 and 12S RNA is inhibited 
by rifampin, but is insensitive to actinomycin D and camptothecin. The 
kinetoplast seems to be a target organelle of several drugs, and it seems 
likely that a basic understanding of the molecular biology of the kineto- 
plast genetic system will aid in the development of a rational 
chemotherapy. 



88 



Leprosy 

Leprosy, a major health problem of the developir^g countries, 
occurs with a very low incidence in the United States. Because of its 
worldwide importance and its usefulness as a model of an immunological 
disease, however, leprosy research continues to be supported by NIAID 
under the auspices of the U.S. -Japan Cooperative Medical Science Pro- 
gram. There are a total of six grants and three contracts. Research being 
supported includes in vivo and in vitro cultivation of M. Leprae, pharma- 
cology of antileprosy drugs, chemotherapy trials and studies of the basic 
immunology of leprosy. 

Inability to grow Mycobacterium leprae and M. lepraemurium in 
cell-free artificial medium (in vitro) has always been a major obstacle to 
leprosy researchers. The lessons learned from a new culture system for 
M. lepraemurim will be applied to the problem of attaining in vitro 
cultivation of M. leprae. 

An NIAID contract with the USPHS Hospital, Carville, has been in 
effect since July 1975, to supply M. /eprae- infected armadillo tissues to 
leprosy researchers (worldwide). The infection rate after i.v. inoculation 
is 50 to 80 percent, and some of the animals inoculated intravenously 
with 10 or more M. leprae are ready to sacrifice for harvest of large 
numbers of organisms in 1 or 2 years. However, some animals are 
apparently resistant to infection. This is analogous to the same phenom- 
enon found in humans; some are resistant and others are susceptible. 
This supply of M. leprae from armadillos in numbers not previously 
available makes it easier to undertake much needed leprosy research. 

A number of new chemical methods have been developed to study 
tissue and plasma levels of the leprosy treatment drugs, Dapsone (DDS) 
and Rifampin (RFM). In the studies of armadillos infected with 
M. leprae, it was demonstrated that dose and plasma levels of DDS were 
linearly related, so these studies provide some information needed for 
chemotherapeutic trials using DDS in infected armadillos. In addition, an 
assessment was made of the use of saliva as a noninvasive means of 
monitoring DDS levels in man; preliminary studies indicated an excellent 
correlation between plasma and saliva levels of DDS. The pharmacokin- 
etic relationships for DDS and RFM that have been established both in 
man and in animals should be applicable and useful for monitoring levels 
in various clinical and experimental situations. 

A major international effort to develop a vaccine against leprosy is 
being carried out in conjunction with the IMMLEP program of the WHO 
Special Programme for Tropical Disease Research. The basic concept for 
this vaccine is that while the majority of patients with leprosy develop a 
tuberculoid form in which cell-mediated immunity develops and self- 
healing ultimately ensues, a minority, generally on the order of 10 per- 
cent, develop the lepromatous form of the disease characterized by a 
selective anergy to antigens of the lepra bacillus. It is in these patients 
that organisms grow to very high concentrations and represent a prime 
source of contagion of this disease. If immunization could prime or 



89 



sensitize for the satisfactory development of a cell-mediated immune 
response to the lepra bacillus upon infection, then possibly a noninfec- 
tious tuberculoid form of infection would ensue. 

As with other research activities supported by NIAID, the extra- 
mural component is by far the largest. Most of the program supports 
free-ranging research, with much smaller efforts in the form of contracts 
channeled into designated areas to provide answers to specific questions, 
develop reagents, or test vaccines, etc. No particular efforts are made to 
coordinate extramural with intramural research, at least over the short 
run. Extramural program officers try to keep in touch with their coun- 
terparts in other U.S. Government agencies that support research in 
tropical medicine, such as the Army and Navy, or private foundations. 

Several additional components of the extramural program (Devel- 
opment and Applications Branch) deserve special mention because they 
specifically involve activities on an international scale or studies in a 
foreign country. These include: 

1. A contract with St. Jude Children's Research Hospital in 
Memphis, Tennessee, for worldwide surveillance of animal influ- 
enza viruses. This is accomplished through a worldwide network of 
collaborating laboratories. The rationale for this program is that 
major antigenic shifts of new human pandemic strains of influenza 
viruses may have resulted from recombination of strains in nature, 
including animal influenza viruses. This project interfaces with the 
U.S.-U.S.S.R. Cooperative Program on Influenza referred to later 
in this report. 

2. The NIAID has had a contract with the Central Public Health 
Laboratory in Helsinki, Finland, since 1974 (renewed for 3 years in 
1977) for evaluation of efficacy of group A meningococcal and 
Hemophilus influenza polysaccharide vaccines in children. 

3. Several viral hepatitis projects in foreign countries are sup- 
ported by contracts with the New York Blood Center. One of 
these involves work on an experimental hepatitis B vaccine in 
chimpanzees in Liberia, Africa, where some of these scarce ani- 
mals are available. The other is a trial of hepatitis B immune 
globulin in the Far East for prevention of transmission of hepa- 
titis B from pregnant carrier mothers to the fetus. 

Individual members of the extramural program serve as members 
of ad hoc or expert committees, panels, etc., for the World Health 
Organization and other agencies with international health activities. 



Intramural Research Program 

The intramural research program for tropical and parasitic diseases 
consists mainly of the research conducted by the Laboratory of Para- 
sitic Diseases (LPD), if the subject area is interpreted very strictly. How- 
ever, since the tropical diseases include rickettsial and other tickborne 



90 



diseases under study at Rocky Mountain Laboratory (RML), as well as 
the virus-caused diarrheal diseases, especially the rotaviruses, which are 
studied in the Laboratory of Infectious Diseases (LID), these two labs 
should be included. The Laboratory of Microbial Immunity (LMI) is 
another intramural unit with a research program that deals with immun- 
ology of parasitic infections in experimental models. Viral hepatitis, 
while not a tropical disease problem in the strict sense, is a very impor- 
tant and substantial portion of the LID research program. Furthermore, 
the viral hepatitis research of LID has extensive international activity, as 
is detailed below. However, for purposes of fiscal analysis, hepatitis is 
not included. 

Legislative authority for intramural research, as with the extra- 
mural program, comes from the Public Health Service Act of 1955 
Public Law 81-692, Title III, Part A, Section 301, and Title IV, Part D, 
Section 431, which deal with creation of additional Institutes of NIH. 
Also Public Law 86-610, Section 2, clause 1, contains the statement "to 
advance the status of the health sciences in the United States and there- 
by the health of the American people through cooperative endeavors 
with other countries in health research, and research training." 

To indicate in somewhat greater detail the nature and extent of 
intramural research programs, several with international involvement are 
described below. These include the following: 

1. Study of gamete immunity in man in Africa by investigators 
of LPD and LI. 

2. Tropical pulmonary eosinophilia and immunology of filariasis 
in India - LPD. 

3. Immunology of Chagas' disease in Brazil — LPD. 

4. International collaboration on hepatitis virus research —LID. 

5. International collaboration on viral gastroenteritis — LID. 



Gamete Malarial Immunity 

In view of the experimental work in LPD on the immunogenic 
effect of avian and simian malarial gametes, which could be demon- 
strated by the failure of gamete-immunized animals to be infective for 
mosquitoes, it seemed important to examine this question in humans in 
an endemic area. In other words, in areas where malarial transmission is 
holoendemic, is there evidence of natural gamete immunity? Several 
investigators of LPD and one from LI studied this question during a stay 
of several months at the United Kingdom's Medical Research Council 
Laboratory in Gambia, West Africa. They found that sera from adult 
immune Gambians did not react with surface antigens on P. falciparum 
gametes using the I FA technique, nor did their sera block cyst forma- 
tion by gametes of P. falciparum in the mosquito. During this same visit 
it was possible to collect additional strains of P. falciparum for future 
work at NIH. 



91 



Tropical Pulmonary Eoslnophllla 

An investigator from LPD made a second annual trip of several 
weeks to Madras, India, for work with collaborators at the Tuberculosis 
Chemotherapy Center and Medical College and General Hospital of 
Madras on tropical pulmonary eosinophilia (TPE) and on filariasis. This 
is an area of the world where TPE and filariasis are both relatively com- 
mon. The former is believed to be a variety of filarial disease in which 
the human host traps the microfilariae that otherwise would circulate 
in the blood. There is no definite proof that TPE is really a filarial in- 
fection, and if so which species (human or animal) of filarial parasite is 
involved, nor do we know the immunologic mechanism by which the 
putative trapping of microfilariae occurs. The condition of TPE is associ- 
ated with very high levels of circulating eosinophils and IgE antibody. 

By using the histamine release reaction prompted by the exposure 
of circulating basophils from peripheral leukocytes of the blood to a 
specific antigen that reacts with IgE coating the surface of the basophils, 
it is possible to test for specificity of the IgE response in these patients. 
The histamine released is measured with an exquisitely sensitive and 
specific radioimmunoassay. These studies have shown that the white 
cells (basophils) of patients with TPE release maximum histamine to 
microfilaria! antigens of human filarial parasites when exposed to vari- 
ous filarial antigens. Thus, it appears that the symptoms and signs of 
TPE can be explained as an allergic (immediate) hypersensitivity reaction 
to human microfilaria! antigens. A number of other important questions 
involving the host immunologic response in filarial infections have been 
raised by this investigation, as well as questions concerning the impor- 
tance of the chronic lung disease which TPE constitutes. This collabora- 
tive project, it should be noted, was initiated as an exploratory P.L.-480 
project and with considerable help from the Fogarty International 
Center. 



Immunology of Chagas' Disease 

The principal manifestation of Chagas' disease is a cardiomyopathy 
that occurs some years after initial infection with the parasite Trypano- 
soma cruzi. Another chronic sequel to infection with T. cruzi is involve- 
ment of the esophagus with dilatation and malfunction that is seen in 
some areas of Latin America and not in others. Both of these features 
of Chagas' disease are important health problems in many regions of 
Latin America, but the prevalence of the disease, as well as presence or 
absence of the megaesophagus, has a spotty distribution that cannot 
easily be explained by different strains of the parasite or degree of ex- 
posure to vector bugs, or by frequency of infection with the parasite, as 
measured by antibody tests. Thus, there are many reasons to question 
whether differences in host response might account for presence or 
absence of chronic disease. With these issues in mind, and because of 



92 



previous laboratory work relating to these problems, several investigators 
of LPD initiated a collaborative project with physicians at the Faculty 
of Medicine of Federal University of Goias in Goiania, Brazil. This is a 
region of Brazil where the megaesophagus and cardiomyopathy of 
chronic Chagas' disease are common. 

Two questions were investigated: one, cell-mediated immune 
response to several different antigens prepared from T. cruzi in patients 
with chronic disease and in appropriate control groups, and second, evi- 
dence of genetic influence over development of chronic Chagas' disease 
by HLA-tissue typing. To carry out the HLA-typing, it was necessary to 
have the assistance of a former research fellow now in Brazil who had 
trained with the tissue typing group at Duke University, as well as 
support from the NIAID extramural program to supply typing trays and 
many of the typing antisera. A final crucial element to this collaborative 
research project was the logistical and financial support of the Pan 
American Health Organization (PAHO). 

Results of the study showed that patients with chronic Chagas 
disease exhibited no unusual cell-mediated immune response to T. cruzi 
antigens. They reacted to the same degree as individuals infected with 
the parasite (positive blood test) but with no evidence of disease. Specif- 
icity of the parasite antigens for blastogenic response was established 
and the most reactive antigen was identified. The HLA-typing showed an 
interesting concentration of one A-locus type among patients with 
chronic disease, as compared to controls, and a relative infrequency of 
another A-locus type. However, this association of HLA-type with 
Chagas' disease was not sufficiently strong for critical statistical evalu- 
ation. It will be necessary to increase the numbers of patients studied 
and this project will be expanded to see if the HLA relationship holds. 



Hepatitis Virus Research 

The hepatitis viruses are ubiquitous agents that are highly endemic 
in the developing parts of the world. They are equally prevalent in 
developing countries situated in tropical and subarctic climates. 

The Hepatitis Viruses Section of the Laboratory of Infectious 
Diseases has carried out an active program of collaborative research on 
viral hepatitis with many groups throughout the world. Among these 
have been studies of the immunopathology of hepatitis B virus infection, 
with a laboratory in Germany, and with investigators in Poland and 
Greece on epidemiology of viral hepatitis. There are collaborative studies 
of new and unique antigens associated with hepatitis B virus infection 
with a worker from Italy and surveys of prevalence of antibody to 
hepatitis virus being done in collaboration with workers in Russia, 
Denmark, and Sweden. 

Other collaborative studies include an examination of epidemics of 
viral hepatitis in India, studies of hepatic cell carcinoma in Taiwan, 
characterization of the hepatitis A virion with an investigator in Japan, 



93 



and the seroepidemiology of type A hepatitis in Kenya. Collaborative 
studies oif viral hepatitis are in progress or in the planning stage in 
Argentina, Brazil, Venezuela, and Costa Rica. 

Other areas of the world where collaborative work on virus hepa- 
titis is being carried out include Australia and islands of the South 
Pacific. Further knowledge on the seroepidemiology of types A and B 
hepatitis in the South Pacific is of particular interest because it might be 
possible to test hepatitis B vaccines in certain islands in the South 
Pacific where their isolated nature offers unique opportunities to test 
the possibility of eradication of hepatitis B viruses from the isolated 
populations. 



Viral Gastroenteritis 

Enteric diseases continue to be a major cause of morbidity 
throughout the world and a major cause of morbidity and mortality in 
the developing countries. The NIAID Laboratory of Infectious Diseases 
is engaged in many collaborative studies with investigators in various 
parts of the world; these studies are aimed at elucidating the etiology of 
gastroenteritis with special emphasis on the role of viral pathogens. 

The LID continues its studies with the World Health Organization 
on the etiology of diarrhea. Thus far, stool specimens from infants and 
young children have been tested from the following countries for the 
presence of rotaviruses and the Norwalk agent: Tunisia, Senegal, Korea, 
Hong Kong, Uganda, Zaire, Malaysia, Singapore, Central African Repub- 
lic, French Guiana, and Sri Lanka. Rotaviruses have been found to be an 
important agent of diarrhea in this age group, whereas the Norwalk 
agent has not. In addition, certain specimens have also been examined 
for the presence of adenoviruses. Only a limited number of paired sera 
are available from this study. 

The LID continues its collaboration with investigators in the 
Cholera Research Laboratory in Bangladesh on the etiology of gastro- 
enteritis. These studies, which are many-faceted, include family studies 
on the etiology of diarrheal illnesses in villages in Bangladesh as well as 
studies of the etiology of diarrheal illnesses in malnourished groups. 

The LID also has collaborated with investigators from Guatemala 
in studying stool specimens from infants and young children from the 
Guatemalan highland village of Santa Maria Cauque. A population of 24 
infants and young children who had been studied previously during the 
first 3 years of life was studied employing newly available methods for 
the occurrence of rotavirus and Norwalk infection. Infection with rota- 
virus was associated with 26 (14.2 percent) of 183 selected diarrheal 
episodes. However, rotavirus infection was documented in over 50 per- 
cent of the dehydrating episodes studied, thus further indicating the 
importance of rotavirus infection in this population. In addition, this 
study indicated that sequential episodes of diarrhea were associated with 
two different rotavirus serotypes. The Norwalk agent was not detected. 



94 



In additional collaborative studies of the LID, the Norwalk agent 
was shown to be associated with a gastroenteritis outbreak in Japan. 
Also, collaborative studies with Australian investigators have confirmed 
the association of Norwalk infection with a large outbreak of gastro- 
enteritis associated with the ingestion of oysters. 

The worldwide prevalence of antibody to the Norwalk agent has 
been investigated collaboratively in a preliminary fashion by studying 
sera from Belgium, Yugoslavia, Switzerland, Ecuador, and Nepal. In 
addition, the role of the Norwalk agent in travelers' diarrhea has been 
investigated by studying specimens from Peace Corps workers in Kenya, 
Morocco, and Honduras. Finally, the LID is engaged in studies of anti- 
body to E. coli LT using an RIA-BL test with serum specimens from 
Peace Corps workers in Kenya, and in inhabitants of Bangladesh. 

In addition to the specific research projects, such as those outlined 
above, which are conducted abroad by NIAID investigators or by their 
direct collaborators, many Institute scientists are involved indirectly in 
international activities. A number of investigators serve on expert com- 
mittees or panels of agencies (WHO, PAHO, Rockefeller Foundation, 
etc.), or are asked to attend scientific meetings that deal with health 
problems of foreign countries. Virtually all of the intramural laboratories 
have Fogarty visiting fellows from foreign countries working in the labs 
who receive research training for a period of 1 to 3 years and then 
return to their country. For example, during FY 1978, there were 39 
such visiting fellows from 15 countries working in the intramural labora- 
tories. Finally, some intramural scientists collaborate with colleagues 
abroad on specific research problems by exchange of information, use of 
special techniques, etc., such as one who collaborates with scientists in 
France on regulation of transcription of SV-40 virus. 

Several of the intramural laboratories serve as reference centers for 
WHO in specific subjects, such as the RML for rickettsial diseases and 
LID for respiratory viruses other than influenza, and for mycoplasms. 

Scientists from foreign countries frequently work in intramural 
laboratories under other auspices than the Visiting Fellow Program. 
Their appointments may be on a more senior level, such as visiting 
associates or visiting scientists, or they may come for short periods as 
guest workers supported by funds from their own country. There were 
18 visiting associates and/or scientists in the Institute during FY 1978 
from 10 different countries. 

Finally, some of the intramural scientists are involved in research 
projects supported by P.L.-480 funds, or funds from bilateral programs. 



The U.S. -Japan Cooperative Medical Science Program 

The U.S. -Japan Cooperative Medical Science Program was initi- 
ated in January, 1965, as the result of a meeting between the Prime 
Minister of Japan and the President of the United States. It was agreed 
that the two countries would undertake a joint cooperative research 



95 



effort in biomedical sciences to improve the health of the people of 
Asia. The disease categories considered to be of particular importance 
included cholera, leprosy, malnutrition, parasitic diseases (schistosomiasis 
and filariasis), tuberculosis, and viral diseases (rabies, dengue hemorrha- 
gic fever, and other selected arbovirus diseases). In 1972, environmental 
mutagenesis and carcinogenesis was added as a seventh category. 

Under Public Law 86-610, the International Health Research Act 
of 1960, the President delegated the responsibility for foreign policy and 
foreign relations of the program to the State Department and for its 
scientific conduct to the Department of Health, Education, and Welfare; 
the latter delegated this responsibility to the National Institutes of 
Health. In 1968, the conduct of the program was transferred from the 
Office of International Research to the National Institute of Allergy and 
Infectious Diseases, where it remains today. 

The U.S. -Japan Cooperative Medical Science Program operates 
within a bilateral governmental framework. Nevertheless, it may involve 
scientists and facilities in third countries and/or collaboration with 
international or other organizations. The relevant regions in Asia, al- 
though not specifically defined, are generally understood to include the 
Republic of Korea on the north, India and Pakistan to the west, and 
other adjacent nations in the broad Pacific basin. 

Each country supports the cost of its own research. At the Nation- 
al Institutes of Health, grants submitted for doing research on the disease 
categories of the U.S. -Japan Cooperative Medical Science Program com- 
pete with all other grants based on scientific merit, and if funded are 
appropriately assigned. However, there is no special fund allocation for 
this program. Contracts are awarded by each Institute based upon need 
and availability of funds. Support for the program is provided by four 
Institutes. Research on cholera, leprosy, parasitic diseases, tuberculosis, 
and viral diseases is supported by the National Institute of Allergy and 
Infectious Diseases. Malnutrition research receives support from the 
National Institute of Arthritis, Metabolism, and Digestive Diseases and 
the National Institute of Child Health and Human Development. Re- 
search on environmental mutagenesis and carcinogenesis is funded by the 
National Institute of Environmental Health Sciences. Total funding for 
grants and contracts during FY 1978 was $11,460,910. A summary of 
these expenditures is found in table 3. 

The notable success of the program, involving close research plan- 
ning and scientific collaboration with many different investigators in 
Japan, may be attributed to careful selection and continuing review of 
research objectives within each of the stated disease categories. During 
calendar year 1978, the joint committee, comprising the United States 
and Japanese delegations, approved the review and evaluation reports for 
the Parasitic and Viral Diseases Panels, and initiated the review process 
for the Environmental Mutagenesis and Carcinogenesis Panels, which will 
be completed in 1979. A very successful symposium on hepatitis was 
held in Tokyo. The joint committee approved in principle the formation 
of a new program on hepatitis pending development of acceptable 



96 



Table 3. U.S. -Japan Cooperative Medical Science Program 
Grants and Contracts FY 1978 





Number 


Dollar 


Number 


Dollar 


Disease Category 


Grants 


Amount 


Contracts 


Amount 


Cholera 


16 


$ 834,000 


4 


$ 309,000 


Environmental mutagenesis 










and carcinogenesis (a) 


48 


3,850,000 


8 


1,500,000 


Leprosy 


6 


577,000 


3 


230,000 


Malnutrition (b) 


12 


1,072,000 


1 


19,000 


Parasitic diseases 


26 


1,676,000 


4 


254,000 


Tuberculosis 


4 


261,000 


2 


134,000 


Viral diseases 


6 
118 


744,910 
$9,014,910 



22 


-- 


Totals 


$2,446,000 




Total Grants and Contracts 


$11,460,910 



(a) Supported by NIEHS ($5,350,000) 

(b) Supported by NIAMDD and NICHD ($1,091,000) 
All others supported by NIAID ($5,019,910) 



guidelines. The Malnutrition Panel's guidelines were revised to include 
the health consequences of differing dietary patterns and food habits. 
This area has application not only to Asia but to all parts of the world. 

Cooperation with the World Health Organization in research on 
schistosomiasis, filariasis, and leprosy has been initiated and efforts to 
strengthen this association continue. The program continues to explore 
ways for developing additional linkages with domestic and foreign organ- 
izations interested in international biomedical research. 



International Centers for Medical Research Program 

The International Centers for Medical Research Program was 
established at the National Institutes of Health under the authority of 
Public Law 86-610, the International Health Research Act of 1960. The 
program operates within this law under Section 2, subsection (1) "to 
advance the status of the health sciences in the United States and there- 
by the health of the American people through cooperative endeavors 
with other countries in health research, and research training." The 
scientific supervision of the ICMR program was under the Office of 
International Health from 1960 until 1968, when this responsibility was 
transferred to NIAID. 

The ICMR grants are funded for 5 years, with the last award being 
made in May 1975. However, continuation is based upon a satisfactory 



97 



annual review of each unit's scientific progress. This program, which has 
been operative since 1960, will be supplanted by a new international 
initiative in 1980. Unlike the present ICMR program, which has included 
areas of research other than infectious diseases and immunology, the 
new program. International Collaboration in Infectious Diseases Re- 
search, will be tightly focused on infectious diseases and the immun- 
ology of these diseases. In addition, infectious diseases research will be 
limited to diseases of health importance in developing countries. How- 
ever, in the past 2 years, the ICMR units have made a concerted effort 
to emphasize infectious diseases research. 

The ICMR program has as its principal objective the provision of 
high quality research and scientific opportunities for Americans in the 
broad fields of tropical medicine and in response to the special oppor- 
tunities existing within each ICMR framework. The length of the re- 
search period overseas is a discretionary concern of the ICMR program 
director and is obviously determined by both the interests of the pro- 
spective investigator and the specific opportunities available within the 
given ICMR unit. Consistently, the emphasis is upon the quality rather 
than the quantity or duration of the research programs. 

The aggregate ICMR units serve as a national resource for utiliza- 
tion by senior, as well as less experienced, scientists to create a compara- 
tively modest pool of investigators with a sustained career interest in 
international or geographic biomedical research. In this regard, the ICMR 
program directors are encouraged to establish a selective, interdisciplin- 
ary scientific program. Their activities encourage and accommodate a 
number of parent university departments other than the one that pri- 
marily sponsors the ICMR operation. Also, interested and qualified 
investigators from other universities may be invited to spend all or part 
of a sabbatical leave performing pertinent research at one of these units. 
As far as is possible, the ICMR core grant is used for research support at 
the offshore ICMR site, rather than at the parent domestic university. 
In FY 1978, the total expenditures of the four ICMR grants was about 
$2,117,000. 

Discussion of the four institutions participating in the ICMR pro- 
gram at present and their respective areas of research interests follows: 

1. The University of California ICMR in San Francisco with its 
overseas site in Kuala Lumpur, Malaysia, is under the direction of Dr. 
Albert Rudnick. Current research interests include continuation of the 
studies of the jungle cycle of dengue and the importance of this jungle 
reservoir as a source of infection in man. Studies in the community 
health section include population dynamics, fetal wastage and infant 
mortality, the behavioral aspects of communicable diseases hazards, 
medical anthropology, and traditional Chinese medical practice. The 
human genetics and hematology section is concerned particularly with 
abnormal hemoglobins. The parasitology section is studying the host- 
parasite interactions in relation to biocontrol of trematode infections in 
snails. 



98 



2. The Johns Hopkins University ICMR in Baltimore has an 
overseas site in Dacca, Bangladesh, and more recently, one in the Pana- 
ma Canal Zone at the Gorgas Memorial Laboratories. With the proposed 
internationalization of the Cholera Research Laboratory, ICMR research 
has been reduced. Only one investigator remains to complete his re- 
search. The major portion of the effect has been transferred to Gorgas. 
The emphasis continues on various aspects of diarrheal research. The 
program director is Dr. Bradley Sack. 

3. The University of Mary/and ICMR in Baltimore and Lahore, 
Pakistan, is under the direction of Dr. Richard Baker. Research in 
Lahore is centered around an integrated program on the genetics and 
field ecology of mosquito vectors. Efforts are directed toward biological 
control of the vectors of malaria and selected arbovirus infections. 

4. Tulane University in New Orleans has an overseas ICMR unit 
in Call, Colombia, which is concentrating its efforts in infectious diseases 
and immunology. The nutritional, behavioral science, and social epidemi- 
ology projects have been or are in the process of being phased out. 
Investigators are pursuing projects in parasitology, bacteriology, and 
virology. This unit is host to Peace Corps volunteers who receive training 
in field work activities. Investigators from other institutions in Colombia 
and the United States are collaborating on a number of research pro- 
jects. Dr. Thomas Orihel is the program director. 



Special Foreign Currency (P.L.-480) Programs 

The P.L.-480 research projects are arrangements by which an 
individual or research group in designated countries is granted the use 
of U.S. -owned local currency from funds generated by purchase of com- 
modities, such as wheat, supplied by the United States. The project is 
linked to an individual or group in the United States, with a designated 
project officer who is expected to supply scientific collaboration, assist- 
ance, or advice for the project. Legislative authority for P.L.-480 pro- 
jects is derived from Section 104(b)(3) of Public Law 480, 83rd 
Congress and Section 37 P.L. 86-610. 

Intramural or extramural scientists serve as project officers for 
P.L. -480 projects. The following projects were in effect during FY 1978: 

1. In Egypt — Tick, vertebrate, and infectious agent interrelation- 
ships 

project officers — Drs. Clifford and Kierans of RML 

2. In Egypt — Tick-borne viruses in vector and host cells 
project officer — Dr. Yunker of RML 

3. In Egypt — Epidemiology of meningitis due to H. influenzae 
project officer — Dr. Hill of Extramural 



99 



4. In Poland - Cytophilic antibody and transfer of skin reactions 
project officer — Dr. Munoz of RML 



Other NIAID Programs Involving International Activities 

The U.S.-U.S.S.R. Cooperative Program on Influenza 

This program is in its fourth year and is essentially a framework 
for scientific communication between the two countries in the subject 
area. It provides for exchange of information, scientific meetings and 
visits by scientists, exchange of virus strains and reagents. Personnel 
from the Extramural Program of NIAID (MIDP) serve as coordinators 
for several of the problem areas of the program. 



Support for the Cholera Research Laboratory 
or U.S.-Bangladesh Agreement 

This program supports research on cholera and related diarrheal 
diseases initiated in 1960 with quite heavy NIAID support and involve- 
ment initially, but with subsequent modifications in the extent and 
nature of the support in recent years. The facility supported is in Dacca, 
Bangladesh (formerly East Pakistan). It is staffed by scientists from the 
host as well as foreign countries, and receives support from the govern- 
ments of the United Kingdom and Australia as well as the local govern- 
ment. 

Funding is provided by a Participating Agency Service Agreement 
(PASA) with the U.S. Agency for International Development (AID). 
Scientific management, administrative support, and supplies are provided 
by NIAID. 

Scientific aspects of the work at the Cholera Research Lab are 
coordinated with other research on cholera and diarrheal diseases sup- 
ported by the extramural program of NIAID. 



Reagents Program for Human Tissue Typing 

The Immunology, Allergy, and Immune Diseases Program (lAIDP) 
of NIAID initiated a program of HLA tissue typing as a central supplier 
of antisera some years ago. This program serves a practical need for 
organ transplantation and does basic immunological research. For ex- 
ample, in FY 1978 the NIAID supplied more than 3,000 vials of HLA- 
typing sera to about 150 non-U. S. laboratories. 

The lAIDP supports periodic international workshops to review 
and disseminate most recent knowledge of the HLA system in man. At 
these workshops new reagents are tested. A serum bank for mouse 
histocompatibility antigens is also maintained by the program for basic 



100 



research in experimental work on genetics of tlie immune response and 
transplantation. These reagents are also supplied to qualified investi- 
gators outside the United States (59 in FY 1978). 

HLA-typing reagents were made available by the reagents program 
to an intramural research project of the Lab of Parasitic Diseases in 
Brazil investigating the possible association of HLA types with chronic 
Chagas' disease. 



The National Institute of Arthritis, Metabolism, 
and Digestive Diseases 



The National Institute of Arthritis, Metabolism, and Digestive 
Diseases (NIAMDD) is responsible for the conduct and support of bio- 
medical research relevant to a wide range of chronic, disabling disorders. 
A number of Institute-funded research activities draw upon the talents 
and investigative expertise of the international scientific community. 
This report highlights the nature and scope of collaborative and individ- 
ual research efforts carried out with NIAMDD support as integral parts 
of the Institute's overall mission. 



Malnutrition Program of U.S.-Japan Cooperative 
Medical Science Program 

Program Background 

The U.S. -Japan Cooperative Medical Science Program was estab- 
lished in 1965 under Public Law 86-610. Medical advisers from both 
countries met in Tokyo in April 1965 and selected cholera, leprosy, 
parasitic diseases, tuberculosis, and viral diseases as initial health prob- 
lems for joint research. Malnutrition was added to the program in 1966. 
Malnutrition was recognized as contributing to increased mortality, 
morbidity, and infections— particularly in infants and children. The 
imbalance of food production and population growth was viewed as 
contributing to malnutrition and as one of the serious health problems 
of people in Asian countries. 

Since its inception, the Malnutrition Panel has concentrated on 
research dealing with problems of protein-calorie undernutrition; anemia; 
vitamin A deficiency; improving low-cost protein foods; toxic substances 
in plant food (mycotoxins); and the effects of malnutrition on physical 
growth, mental development, and performance. The panel has held 
symposia almost every year on special priority topics as stated in joint 
scientific guidelines. These meetings have been attended by many scien- 
tists from other countries In addition to the United States and Japan. 



101 



The priority areas have been revised and modified from time to 
time, depending on advances in research and need for change of direc- 
tion and emphasis. Cooperation with other agencies having similar inter- 
est in malnutrition research has also been actively pursued. Liaison 
members of the U.S. Malnutrition Panel include representatives from the 
United States Agency for International Development, Pan American 
Health Organization, and other NIH Institutes. In addition, staff from 
other agencies (United States Department of Agriculture, Health and 
Nutrition Examination Survey, and Center for Disease Control of the 
U.S. Public Health Service) have been invited to some panel meetings. 

The Institute is endeavoring to strengthen its international nutri- 
tion research activities that are involved in the U.S. -Japan Cooperative 
Medical Science Program. Support given to the Malnutrition and Anemia 
Center at Chiang Mai, Thailand, for 10 years has produced a facility 
through which many aspects of malnutrition can be studied much more 
effectively than in the United States. 

Since 1965, the Malnutrition Program of the U.S. -Japan Cooper- 
ative Medical Science Program has been the primary avenue through 
which international research activities in nutrition are supported. Accom- 
plishments of the U.S. Malnutrition Program in FY 1978 included the 
support of research projects in previously identified priority areas, 
individual and joint panel meetings, symposia, and publications. 

Specific research projects, carried out abroad among populations 
with severe nutritional deficiency diseases, are designed to find solutions 
to complex malnutrition problems. Since only half of the earth's popula- 
tion is able to maintain an adequate diet, there is a critical need for 
research to find economically feasible ways and means to transform 
marginal nutrition and overt nutritional deficiency to adequacy. 

Traditionally, the Institute has conducted such nutrition research 
in developing countries because of the availability of large population 
groups afflicted with specific nutritional deficiencies that can be readily 
studied. The results are twofold: the research may stimulate emergence 
to nutritional self-sufficiency from mere subsistence in developing 
countries and may also add knowledge of normal nutrition and nutri- 
tional deficiencies that will benefit the U.S. population. 

The startling realization that malnutrition also exists within our 
own population lends an element of expediency to nutrition research. 
By providing scientific know-how for effective use of economical native 
protein sources, these programs also discourage dependency of develop- 
ing countries on more progressive countries for expensive protein-rich 
foods while enabling them to make inroads against protein malnutrition. 

Based on the availability of funds, the U.S. Malnutrition Panel 
fulfills the following objectives: (1) supports scientific projects; (2) 
organizes, funds, and conducts scientific meetings in the United States; 
(3) provides financial support to the U.S. Panel members and consult- 
ants attending meetings related to the program; and (4) provides staff 
and operating costs to the U.S. Secretariat. The Japanese ministries of 



102 



Health and Welfare and Education assume a similar responsibility for 
their counterpart activities, i.e., research projects, meetings held in 
Japan, panel members and consultants, and the Japanese Secretariat. 

The total NIH support for nutrition research under the U.S.- 
Japan Program in FY 1978 was $1.07 million. NIAMDD provided 
$381,779, while the remainder was awarded from the National Institute 
of Child Health and Human Development. In addition, the NIAMDD 
supported the Joint U.S. -Japan Panel Meeting and International Confer- 
ence on Behavioral Effects of Energy and Protein Deficits held in Wash- 
ington, D.C., in late 1977 by an estimated amount of $44,024. The 
International Rice Research Institute was awarded a contract of $18,834 
to complete the nutritional evaluation of improved high-protein rice 
recently developed in the Philippines under a long-term contract from 
NIAMDD. 

The activities of the panel, administered by the NIAMDD, are a 
part of the overall U.S. -Japan Cooperative Medical Science Program 
administered by the National Institute of Allergy and Infectious Diseases, 
NIH. The Department of State provides formal channels to the Japanese. 
The overall USJCMSP has both U.S.- and Japanese-appointed delega- 
tions, which are jointly responsible for the programs. 



Research and Related Activities 

Principal aspects of international health cooperation are: 

1. Support of research projects that fulfill the current and 
updated research objectives of the U.S. Malnutrition Panel: 

(a) influence of environmental and host factors on nutritional 
requirements; 

(b) health significance and methods of preventing iron de- 
ficiency; 

(c) interaction of nutrition, immune competence, and 
infection; 

(d) health consequences of different dietary patterns and 
food habits. 

2. Support of workshops and conferences to further research 
important to solving the malnutrition problems of Asian 
countries. 

3. The Joint U.S. -Japan Malnutrition Panels meet annually, 
alternating between the United States and Japan. The meeting 
for FY 1978 was held in Washington, D.C., on November 29, 
the day preceeding the 3-day conference. Simultaneous trans- 
lation into English and Japanese was provided for the 4 days. 



103 



Research Progress: FY 1978 

Research on bladder stone disease in children in Thailand involves 
the daily supplementation of 60 mg of inorganic phosphorus per kilo- 
gram body weight. Although it is too early to draw conclusions, no 
significant difference has been observed in the number of subjects who 
developed bladder stone disease symptoms between the treated and the 
placebo groups. However, the percentage of subjects who developed 
severe symptoms associated with this condition was significantly higher 
in the untreated group. 

Evaluation studies compared the nutritional' value of a high-protein 
vs. conventional low-protein milled rice at levels supplying the same pro- 
tein intake. Nitrogen balance studies were performed in four Filipino 
children, eight convalescing Peruvian children, and five Taiwanese men. 
The genetically improved rice containing more total protein was found 
to be comparable or only slightly inferior in apparent digestibility and 
apparent nitrogen retention to low-protein conventional rice. This work 
shows that the improved high-protein variety has a net protein utiliza- 
tion comparable to that of conventional rice, per unit of protein. Thus, 
growing children, who require more protein than can be provided with 
native diets based on conventional rice, fed the rice containing the 
higher protein level would receive considerably more utilizable protein. 

Recently, the Malnutrition Panel has redefined its established 
objectives in accordance with its research progress in these areas. In 
addition, the panel has begun serious examination of the potential 
scope of its new objective, "health consequences of different and chang- 
ing dietary patterns and food habits." This topic was the basis for plan- 
ning a joint U.S. -Japan Malnutrition Workshop in December 1978 
(FY 1979). 



U.S.-U.S.S.R. Cooperative Program in Arthritis 

A cooperative study of arthritis organized under this program is 
a fourth major collaborative project in the health sciences between the 
United States and the U.S.S.R. Through a series of bilateral exchanges 
of scientific personnel, the program emphasizes clinical studies of the 
treatment of systemic lupus erythematosus (SLE) and rheumatoid arthri- 
tis. Since 1974, ten major meetings have been held, including the most 
recent meeting in Moscow, October 16-18, 1978. These meetings are 
supplemented by the exchange of reprints and lecture materials, as well 
as by discussions of preliminary results and future projects. 

The cooperative program in arthritis has its origin in the U.S.- 
U.S.S.R. Health Exchange Program of 1972, a joint agreement designed 
to improve collaboration between the two countries in the field of pub- 
lic health and medical science. On September 7, 1973, arthritis became 
the fourth area of concentration in the program through a joint an- 
nouncement of then-Secretary of HEW Caspar W. Weinberger and Soviet 



104 



Minister of Health Boris V. Petrovsky. In FY 1978, NIAMDD funding in 
support of the program totaled $234,809. 

In December 1976, the United States and the U.S.S.R. began 
their first cooperative clinical trials in the field of arthritis. Physicians in 
both countries are now conducting identical studies on the use of 
D-penicillamine in rheumatoid arthritis. Clinical trials in Great Britain 
have supported its efficacy in treating serious forms of the disorder. On 
November 8, 1978, D-penicillamine was approved by the U.S. Food and 
Drug Administration for the treatment of severe, active rheumatoid 
arthritis that has failed to respond to more conservative treatment. In 
the present U.S. -U.S.S.R. cooperative study, lower doses of the drug are 
being compared for effectiveness with the generally prescribed higher 
doses in an effort to reduce the incidence of adverse side effects. 

Dr. Israeli Jaffe of the New York Medical College and Drs. John 
Decker and Paul Plotz of the Arthritis and Rheumatism Branch of the 
NIAMDD are coordinating the U.S. cooperative trial in four New York 
medical schools. In the Soviet Union, studies are under way at the 
Institute for Rheumatism of the Academy of Medical Science in Moscow 
under the direction of Professors M.G. Astapenko and E. Agababova. 
The effectiveness of treatment over a 1-year period will be evaluated, 
and analysis of the data will begin in January 1980. • ■ 



Research Emphasis 

The Fifth Working Meeting of the U.S. -U.S.S.R. Cooperative 
Program was held in October 1978 in Moscow. At this session, the 
program participants discussed progress in clinical studies of SLE, 
rheumatoid arthritis and juvenile rheumatoid arthritis, progressive sys- 
temic sclerosis (scleroderma), and hand function in rheumatoid arthritis. 
In addition, virological and immunological studies will continue to 
explore the mechanisms at work in SLE, rheumatoid arthritis, and pro- 
gressive systemic sclerosis. 

Future work plans for these areas emphasized exchange of scien- 
tists, data collection and pertinent technical information, and the con- 
tinuation of clinical studies of patients with these disorders. The 
U.S. -U.S.S.R. program collaborators will meet in the United States in 
the spring of 1980 to assess results of ongoing studies and to discuss 
future plans for expansion of research in certain problem areas. 



Bone Diseases Program 

The Bone Diseases Program of NIAMDD currently supports a 
long-term research effort headed by investigators at the Hadassah Uni- 
versity Hospital in Jerusalem, Israel. These scientists are studying the 
effect of prolonged administration of a combination of calcium, phos- 
phate, and fluoride salts on bone structure and density in middle-aged 



105 



patients with osteoporosis. Another aspect of this effort is an investiga- 
tion into the relationship between long-term levels of intake of various 
dietary components and the prevalence and severity of osteoporosis 
among patients with different ethnic backgrounds, geographic origins, 
and dietary customs. The unique population makeup of this country 
provides an optimal opportunity for this type of study. 

Also included in this project is development of new techniques of 
early diagnosis of osteoporosis through bone densitometry sophisticated 
enough to discern minimal changes in bone density particularly in the 
spinal vertebrae. A study of the possible prophylactic and therapeutic 
roles of the recently defined biologically active metabolites of vitamin D 
rounds off this comprehensive project in osteoporosis. 



Kidney, Urologic, and Blood Diseases Program 

The Kidney, Urologic, and Blood Diseases Program of the NIAMDD 
currently supports in foreign countries three research grants totaling 
$132,855, and ten research and service contracts in the amount of 
$572,964. 

Among the grantees, investigators at the Mahidol University in 
Bangkok, Thailand, are analyzing genetic defects in the thalassemias and 
related hemoglobinopathies, and studying interactions between the vari- 
ous genes and between genes and environmental factors. 

Another grantee investigator. Dr. Robert Williamson, of St. Mary's 
Hospital Medical School at the University of London, is a leading 
international expert in the control of hemoglobin biosynthesis and 
genetics. He is studying the composition of genes determining the struc- 
ture of hemoglobin, and the interaction of those genes with neighboring 
genetic material. 

Research carried out by NIAMDD contractors abroad extends 
from basic chemical studies to an unusual group of investigations con- 
ducted by three different research teams in Germany to compare the 
efficacy of postdilution hemofiltration with conventional hemodialysis. 
The former method of treating patients with chronic renal insufficiency 
was developed by Dr. Eduard A. Quellhorst of the Nephrological Center 
Niedersachsen in West Germany. It is being studied there, in conjunction 
with studies in the United States, because of the existence in Germany 
of a base of research (patients regularly treated with hemofiltration and 
hemofiltration machines) in this field available nowhere else in the world. 

Another example of research supported abroad under contract is 
the screening program on populations of uremic patients and subsequent 
analysis of "middle molecule" (a suspected group of toxins in anemia) 
data that are being studied in relation to diagnosis, protein intake, 
incidence of various uremic and nonuremic complications, different 
biochemical variables in plasma, residual renal function, and dialysis 
index. The Institute has funded this work by Dr. Jonas Bergstrom, who 
is known worldwide for these important investigations. 



106 



The work of Dr. Dimitrios G. Oreopoulos of Toronto Western 
Hospital in Canada is another contract-supported investigation abroad. 
Dr. Oreopoulos treats the largest patient population maintained by peri- 
toneal dialysis in the world. NIAMDD-sponsored investigations of the 
novel technique known as continuous ambulatory peritoneal dialysis 
(CARD) were contracted with him because of his great experience, 
remarkable and original innovations, and access to such a large popula- 
tion of suitable patients. CARD appears to be on the brink of becoming 
a significant mode of maintenance treatment in chronic renal failure, 
and the studies of Dr. Oreopoulos' team are now directed toward lower- 
ing the incidence of peritonitis, defining the ideal composition of the 
dialysate for this therapy, and improving the connection through which 
solution is introduced into the abdominal cavity. 



Diabetes, Endocrine and Metabolic Diseases Program (DEMD) 

Since the passage of the National Diabetes Mellitus Research Edu- 
cation Act in 1974, emphasis on this segment of the Institute's overall 
research effort has increased significantly. While not in the context of 
one specific program, 18 international research projects were supported 
in FY 1978 by the Institute's Diabetes, Endocrine, and Metabolic 
Diseases Program in the amount of $752,685. 

In addition, the DEMD program supported a workshop on diabetes 
at the international level. A major problem in the assessment of its 
impact is the lack of a satisfactory diagnostic and classification scheme 
for the various forms of diabetes. To address this issue, the Institute's 
National Diabetes Data Group sponsored, in FY 1978, an international 
work group that formulated a consensus on a functional classification 
of diabetes, and on appropriate uniform criteria and nomenclature to be 
used as a guide for clinical and epidemiological research information. 
This classification has been widely circulated among the international 
diabetes community for comment. 



FY 1978 Foreign Awards in the Diabetes, Endocrine, 
and Metabolic Diseases Program 

Visiting Scientists Program 

A description of the international activities of NIAMDD would 
be incomplete without reference to the very important impact exerted 
by the appointment of qualified scientists from abroad to work in the 
Institute's laboratories and clinics in Bethesda for various periods of 
time, and reciprocal arrangements for NIAMDD scientists to visit and 
work in collaborating laboratories and clinics abroad. 

Some of these arrangements fall into the framework of formal 
bilateral scientific collaboration agreements between the United States 



107 



and other countries, primarily in Europe; others represent longstanding 
informal arrangements between a number of laboratories throughout the 
world and the intramural program of NIAMDD. This exchange of high- 
caliber scientists across national boundaries with constant opportunities 
for cross-fertilization of new ideas and biomedical techniques has been 
mutually beneficial for many years and is expected to continue provid- 
ing significant scientific dividends in the future. 



Outlook 

The NIAMDD plans to continue its international involvement in 
research in order to capitalize on the scientific expertise, as well as the 
unique research settings, available throughout the world. Only through 
open communication and pooling of research knowledge can we hope to 
control, prevent, and ultimately eliminate the many diverse disorders 
that fall within the Institute's investigative responsibilities. 



National Institute of Child Health and Human Development 



Introduction 

The NICHD views the development of international relationships 
in the biomedical and behavioral sciences as crucial to the pursuit of 
new knowledge in the field of maternal-fetal-child-family development. 
The Director of the Institute serves as the focal point for all interna- 
tional activities, which range from cooperative bilateral health agree- 
ments (to facilitate scientific exchange) to support of and participation 
in international meetings, conferences, and seminars. During the report- 
ing period, the Institute supported 31 international research projects 
totaling $2,039,060; 12 program projects totaling $601,725; 6 research 
contracts totaling $486,175; and 2 intramural projects totaling $49,000. 
A grand total of 51 projects were supported at a total of $3,175,960. 
These programs were funded through the Institute's Center for Research 
for Mothers and Children (CRMC), Center for Population Research 
(CPR), Epidemiology and Biometry Research Program (EBRP), and 
Intramural Research Program (IRP), and are discussed in detail in the 
section that follows. 



Major Programs and Activities 

Epidemiology and Biometry Research Program (EBRP) 

The Biometry Branch of the EBRP currently oversees two bilateral 
health projects. 



108 



The first is a contract and collaborative research project under 
P. L.-480 funding with the Mother and Child Institute of Warsaw, Poland. 
The project, initiated in April 1976 and completed in December 1978, 
involves a study of the effects of induced abortion on subsequent preg- 
nancy outcome. Thus far, analyses have focused on modes of termina- 
tion of pregnancy, birthweight of live boms, age of mother, education, 
smoking, height, types of medication taken during pregnancy, number of 
previous pregnancies, abortions, and interruptions. Since therapeutic 
abortion is the predominant method of birth control in many countries 
and is increasing in frequency in the United States, the effect of abor- 
tion procedures on subsequent pregnancy outcome is a question of 
utmost importance that deserves to be answered. 

The second is a contract and collaborative research project with 
the University of Trondheim, Norway. The project, "Outcome of Suc- 
cessive Pregnancies for Norwegian Women, 1967-1976," was initiated in 
August 1978 and is still in progress. The contract relies upon a unique 
data base to study some statistical aspects of repeating premature or 
mature births in a well-defined national cohort of mothers. This study 
will contribute to research aimed at elucidating factors that predispose 
to preterm or low birth weight delivery. Infant mortality will be studied 
as it relates to prematurity and the tendency to repeat similar gestation- 
al age and birthweight in subsequent deliveries to the same mother. This 
tendency to repeat premature delivery is one of the strongest predictive 
associations known from previous studies of the epidemiology of 
prematurity. 



Center for Population Research (CPR) 

The CPR is participating in numerous important contracts and 
grants involving international research activities. During FY 1978, the 
center's international projects totaled 34. Examples of the major inter- 
national research projects supported by CPR in FY 1978 are summarized 
below. 

Investigators at Johns Hopkins University are conducting a study 
in Taiwan to determine whether any association exists between oral 
contraceptive usage and increased risks of stroke among married women 
of childbearing age in a developing country. 

A grant to the University of Southern California is supporting a 
study to determine the effect of family size and child spacing upon the 
health and social development of children and their mothers, involving a 
Danish population of 9,000 children born in Copenhagen between 1959 
and 1961. 

Using data from Canada, the Dominican Republic, Colombia, and 
Chile, investigators at Northwestern University conducted a study to 
develop and test econometric models relating to fertility and female 
labor force participation over the life cycle. The aim of the study was to 
provide an econometric framework for the analysis of population prob- 
lems. The final report is being completed. 



109 



A grant to the Transnational Family Research Institute is support- 
ing a 1-year study to ascertain sociodemographic characteristics and 
frequency distributions associated with specific patterns of pregnancy 
resolution for all wonrien in Denmark ages 13-18 and, where possible, 
their male partners. Nationally representative data on the determinants 
of patterns of adolescent pregnancy resolution are difficult to obtain in 
the United States, but such information is available in Denmark through 
the Danish Abortion Register, Birth Register, and Population Register. 

Investigators at the University of Southern California are conduct- 
ing a study to prepare a catalog of statistical information on childless- 
ness and one-child fertility found around the world. A comparative 
analysis of data from the United States and a variety of other countries 
is being made, using demographic and social variables. 

A grant to the East-West Center in Hawaii is exploring trends and 
differentials in the timing of births using data from two national surveys 
of Korea and the Philippines. The purpose of the study is to describe 
and analyze the socioeconomic and cultural determinants of child spacing 
in two economically developing countries. 

Investigators at Cornell University are involved in a 2-year study to 
examine the differences and similarities of the effects of community 
variables and individual family characteristics on fertility and mortality 
in Costa Rica, El Salvador, Guatemala, Honduras, and Nicaragua. The 
project will analyze economic factors in fertility decision-making and in 
infant and child mortality, relating all these factors to demographic 
transition in Central America. 

A 2-year grant to the University of Michigan supports a study on 
fertility and family planning in Taiwan. The project is examining con- 
tinuities and changes in the relationship between measures of moderniza- 
tion and fertility at the macro level, and changes in attitudes affecting 
reproductive behavior at the individual level. 

Investigators at Northwestern University are conducting studies on 
the causes and consequences of high-level migration from the Philippines 
to the United States. In recent years, the Philippines has been the single 
largest contributor of professional and technical worker-immigrants to 
the United States. The study will examine trends in migration from the 
viewpoint of the individual. 

A grant to the Massachusetts Institute of Technology is assessing 
the impact of government policies and programs on out-migration from 
rural communities in developing countries, using Mexico as a case study. 
Investigators are examining interrelationships between internal and inter- 
national migratory movements by identifying the social, economic, and 
political consequences of Mexican migration to the United States, both 
legal and illegal. 

In addition to the contracts and grants research program, the CPR 
has established a collaborative working relationship with the U.S. 
Agency for International Development (AID) and the World Health 
Organization (WHO). This involves convening meetings for sharing pro- 
gram information and plans, exchange of progress reports, and staff 



110 



consultations; providing testing for long-acting drugs that have been 
synthesized by WHO contractors; and supporting joint studies. 

The director of CPR chairs the Interagency Committee on Popula- 
tion Research that coordinates population research activities supported 
by Federal agencies and fosters the exchange of information among the 
member agencies. 



Center for Research on Mothers and Children (CRMC) 

During FY 1978, the CRMC engaged in 11 international research 
projects, summarized below by program area. 



Human Learning and Behavior Branch (HLBB) 

The NICHD supports a series of cross-language studies comparing 
the processes that underlie the reading of English and Serbo-Croatian, 
the language of Yugoslavia. The research is designed to increase our 
understanding of how the processes of reading interrelate with the 
language system that a person has at the time reading is acquired. This 
research has been conducted in close collaboration with New Haven, 
Connecticut, based American scientists who are also supported by the 
NICHD. 

This study and others conducted in Yugoslavia were recently 
reported at a cross-language conference held at NIH and sponsored by 
the NICHD and the Fogarty International Center. 



Pregnancy and infancy Branch (PI) 

The PI Branch of CRMC supported 10 international research 
projects. 

Investigators at the University of Melbourne, Australia, conducted 
chemical studies of relaxin and its receptors to delineate the many as- 
pects of the chemistry and biological reactivity of the hormone relaxin, 
which has recently been purified. Studies on the amino acid sequence of 
the various forms of porcine relaxin found in pregnant porcine ovaries, 
as well as the sequence of prorelaxin, were conducted. 

A grant to Murdoch University, Australia, supported studies on 
delayed implantation and development in marsupials. Studies were con- 
ducted to determine the role of uterine secretions and extrauterine sub- 
stances, especially hormones, in the initiation and maintenance of fetal 
development; and the correlation of the phases of embryogenesis with 
the metabolism of the embryo, especially in relationship to embryonic 
diapause and subsequent reactivation of the embryo. 

Investigators at the University of Bristol, England, conducted 
studies on the control of breathing before and after birth. Mature 



111 



exteriorized sheep fetuses were studied to identify the level and type of 
central inhibition that renders respiratory and nonspecific stimuli inef- 
fective. They also hoped to identify the principal drive to ventilation in 
the fetuses. 

A grant to McGill University, Canada, supported studies on forma- 
tion, metabolism, and the role of hormones in pregnancy. This project 
studied the mechanisms that control heme synthesis in human fetal liver 
by cell culture techniques. It also investigates the factors that are 
responsible for the induction of surfactant formation in fetal lung. 

Investigators at the University of Manitoba, Canada, examined 
membrane receptors for placental lactogens of several different species, 
PRL, GH, and insulin. The major thrust was to illuminate the dynamic 
state of receptors in target tissues and to establish more fully the im- 
portance of receptors in hormone action. 

A grant to the Baker Medical Research Institute, Australia, exam- 
ined respiratory system development and sudden infant death. This 
study was conducted to elucidate the chemical and neural control of the 
respiratory system of fetal lambs in utero, during birth, and in the 
immediate postnatal period, and the influence of respiratory activity and 
lung liquid flow on the maturation of the respiratory system. 

Investigators at the University of Toronto, Canada, conducted a 
correlated neurophysiological and morphological study of neuronal 
mechanisms possibly involved in or causative of the sudden infant death 
syndrome. 

A grant to the University of Edinburgh, Scotland, supported the 
study of genetic analysis of embryonic limb growth in mice. Investi- 
gators attempted to pin down more precisely the differences between 
high body weight and low body weight lines of mice that have been 
produced by artificial selection. The study examined limb growth 
parameters in mice that were selected for large and small body size in 
the hope of identifying physiological correlates of genetic differences in 
growth rate. 

Investigators at the University of Trondheim, Norway, conducted 
studies on the effects of maternal age, parity, marital status, and spacing 
of births on the survival of births within different sibship sizes. In addi- 
tion, the investigators made a comparison of the causes of infant death 
in Norway and in selected U.S. states. 

A grant to the University of Oxford, England, supported the devel- 
opment of animal models for studies of SIDS. Pursuing the lead that the 
apnea may be triggered in young lambs by certain liquids such as water, 
cow's milk, or human milk, the investigators discovered that two types 
of mucosal water-sensitive units were found in the superior laryngeal 
nerves. These two types of mucosal units were found also in cats and 
Rhesus monkeys at each stage of maturity. The investigators found that 
slowness of heart beat and hypertension appear to be chiefly mediated 
via pathways other than the superior laryngeal nerves. 



112 



Developmental Biology and Nutrition Branch (DBN) 

In FY 1978 the DNB Branch supported six international research 
studies that are summarized below. 

Investigators at Johns Hopkins University are conducting studies 
on the role of staple food in infant nutrition. One project is studying 
groups of children in Peru to determine how well certain locally avail- 
able staple foods (potatoes, wheat) satisfy the energy and protein needs 
of infants with diverse nutritional requirements. 

A grant to the Medical College of Wisconsin supported work on 
malnutrition and development of physical fitness in children. A group of 
males ages 6-16 are being studied in Call, Colombia, to determine their 
work capacity and nutritional status. The three groups studied repre- 
sented high socioeconomic urban, low socioeconomic urban, and low 
socioeconomic rural children. This study will provide a quantitative 
assessment of the influence of poor nutritional history on the develop- 
ment of physical work capacity, and an excellent opportunity to learn 
the impact of urban life on the growth and development of children. 

Investigators at the University of California at Los Angeles con- 
ducted a study at Nairobi, Kenya, on the relationship of early malnu- 
trition, immunologic competence, and immunity to measles. In this 
project 75 mother-infant pairs in which the baby suffered intrauterine 
growth retardation and 75 control pairs are being studied to determine 
the immunologic and nutritional correlates of varying degrees of intra- 
uterine malnutrition, and the incidence, causes, and consequences of 
measles vaccine failure. Preliminary results show decreased cellular im- 
munity, not only in the group of infants weighing less than 2,500 grams 
at birth, but also in the group weighing 2,501 to 2,800 grams. 

A grant to the Harvard School of Public Health, involving a 
collaborative effort with the University of Giessen (Germany) and the 
Nutrition Division of the Colombian Institute of Family Welfare, 
supports a study on malnutrition and its effects on psychological de- 
velopment in Bogota, Colombia. This study examines the effects of 
environmental deprivation and malnutrition in late pregnancy and during 
the first 3 years of life on physical development, psychomotor functions, 
and cognitive development. Results indicate that the nutritional supple- 
ment provided was associated with increments in weight gain during the 
last trimester of pregnancy and in birthweight of male babies. The 
supplemental program was also associated with a decrease in the rate of 
stillbirths and neonatal and perinatal mortality. During the first 18 
months of life, the supplementation resulted in significant increments in 
the rate of weight and height gains. Improvement in locomotor and 
cognitive measurements were obtained in a stimulated group of children. 

Investigators at the Medical University of South Carolina con- 
ducted a study on genetic childhood diseases and aging, for the purpose 
of determining immunologic approaches to the detection of disease. In 
one subproject, antibodies to human cartilage were detected in the 
serum of leprosy patients from two different geographic areas of Papua, 



113 



New Guinea. As yet, it is not clear to what extent these antibodies are 
implicated either in the pathogenesis or the complications of leprosy or 
in the prolongation and intensification of inflammatory reactions involv- 
ing collagen at sites such as the skin, nerves, and glomerular basement 
membrane. 

A grant to the Medical College of Virginia supported a major study 
in human genetics using panels of twins to investigate genetic compo- 
nents of diseases, behaviors, and twinning. A previous study of Danish 
twins by the principal investigator showed that a female twin exposed to 
a male twin in the uterus had a higher risk of developing ovarian cancer. 
The researchers expanded that analysis, using a large tumor registry at 
the Medical College of Virginia. A Norwegian Twin Registry will also be 
used to define genetic, maternal, and environmental factors in the pro- 
duction of fetal wastage and congenital defects. An attempt will be 
made to assess genetic components as well as environmental components 
by comparison of families of twin mothers with families of twin fathers. 



Mental Retardation and Developmental Disabilities Branch (MRDD) 

During the reporting period the MRDD Branch engaged in 3 
international research projects that are summarized below. 

A grant to the New York Blood Center is supporting a 5-year 
research program in cytogenetics involving correlations of karyotype and 
phenotype on patients. The laboratory has facilities available for training 
of visiting scientists from abroad in the area of cytogenetics. 

A 5-year grant to Albert Einstein College of Medicine supports a 
study to examine the socialization of young people who have different 
types of mental retardation, with particular emphasis on the transition 
from childhood to adulthood. The present study uses a defined popula- 
tion of retarded subjects studied in Aberdeen, Scotland, 10 years ago. 
The results of this study will aid in understanding the problems encoun- 
tered by older mentally retarded individuals in adapting to society, and 
the socialization processes that enhance or detract from later life 
adjustment. 

An extension of a study initiated by the Youth Aliyah, Jerusalem, 
Israel, on cognitive functions of retarded early adolescents is being 
conducted in the United States through Institute support of MR research 
centers. This research activity will contribute knowledge on educational 
interventions that can be introduced to prevent or reverse cognitive 
impairment resulting from depriving life experiences. 



Intramural Research Program (IRP) 

During the reporting period, the IRP also participated in inter- 
national research activities. The NICHD, under the authority of the 
U.S. -Polish Bilateral Health Agreement, entered into a collaborative 



114 



research agreement with the National Institute of Mother and Child, 
Warsaw, Poland. Three Polish scientists visited the NICHD to undertake 
collaborative research activities. Dr. K. Mataszeuiska and Dr. A. Pickar- 
czyk worked with Dr. Philip Nelson in the Laboratory of Developmental 
Neurobiology; and Dr. A. Sito worked at the Moore Clinic at Johns 
Hopkins University investigating clinical genetics. Dr. Philip Nelson, 
NICHD, traveled to the National Institute of Mother and Child, Warsaw, 
Poland, to undertake collaborative research activities. 



Director's Activities 

The Director of the Institute participated in "Priorities in Man- 
power for Child Health Services in Developing Countries," a workshop 
sponsored by the 15th Congress of the International Pediatric Associ- 
ation (IPA) in New Delhi, India. He served on the Executive Committee 
of the IPA, as well. 

The Director served as a consultant to the Division of Family, 
Maternal, and Child Health of the World Health Organization (WHO). 
The division meeting was held in Geneva, Switzerland, June 15-18, 
1978. 

A publication from an earlier Congress of the International Organi- 
zation for the Study of Human Development (lOSHD) appeared during 
FY 1978: Mutations: Biology and Society edited by Dwain N. Walcher, 
Norman Kretchmer, and Henry L. Barnett. 

The Director of the Institute, who serves as chief of the Develop- 
mental Gastroenterology and Nutrition Section, Intramural Pregnancy 
and Infancy Research Branch, initiated an exchange program to bring 
two foreign fellows to the NICHD. They are Dr. Shimon Walter Moses, 
Faculty of Health Sciences, Ben-Gurion University of Negev, Beersheba, 
Israel, and Dr. Francis D. Raul, National Institutes of Health in France. 



Institute Trends in International Activities 
and Proposed New Directions 

It is the intent of the" NICHD to continue to support international 
research activities to investigate health problems that are in concert with 
the mission of the Institute — to improve the health and well-being of 
mothers and children. Many of the problems associated with pregnancy, 
infancy, and childhood overlap geographic boundaries. Solutions to 
these problems may be found in collaborative research activities between 
scientists involved in similar investigative research, both nationally and 
internationally. As new ties are initiated with developing countries, the 
Institute hopes to engage in an exchange of scientific information to 
facilitate the acquisition of new knowledge. Our awareness of shared 
world health problems has led us to conclude that there is a critical 



115 



need for an expansion of international research activities aimed at 
ameliorating and/or preventing morbidity or mortality. These efforts 
would serve to strengthen and enhance the quality of life for all. 



National Institute of Dental Research 



The National Institute of Dental Research continues to engage in, 
and actively support, international scientific collaboration and contacts 
directed toward the common global goal of dental disease prevention 
and control. 

Emphasis has been placed on Institute staff participation in, and 
financial support of, international meetings and the publication of their 
proceedings, the funding of foreign grants, and provision of research 
opportunities for visiting scientists. These endeavors result in mutual 
benefits leading to the advancement of dental research knowledge and 
have enabled individual scientists to make a personal contribution to 
international dental public health. 

During FY 1978, the National Institute of Dental Research finan- 
cially supported three international meetings: 

Tenth International Biomaterials Symposium 
Second World Congress on Pain 

International Association for the Study of Pain and Satellite 
Conference on Oral-Facial Pain 

Institute staff members presented research reports, chaired scien- 
tific sessions, served as committee members, or participated as discussion 
panelists at 35 international meetings listed below. 

13th International Congress of Genetics 
6th European Teratology Society Congress 
13th International Embryological Congress 
International Conference on Electrolyte Precipitation in 

Aqueous Solutions 
International Symposium in Pediatric Stomatology 
11th International Congress on Nutrition 
European Federation of Connective Tissue 
International Congress for Microbiology 
2nd World Congress on Pain 
7th International Biophysics Congress 
6th International Conference on Magnetic Resonance 
International Symposium on New Dentifrices 
Federation Dentaire Internationale 



116 



14th Annual Meeting of European Associations for the Study 

pf Diabetes 
International Symposium on Collagenase in Normal and 

Pathological Connective Tissues 
Symposium on Studies in Joint Disease 
4th European Immunology Congress 
Norwegian Section, Scandinavian Society of Pedodontics 
Symposium on Pathobiology of Viral Diseases 
7th International Congress of Reticuloendothelial Society 
12th Leukocyte Culture Conference 
International Conference on Periodontal Research 
European Organization for Caries Research 

Pan American Health Organization 

3rd International Workshop on Calcified Tissues 

South American Biochemical Congress 

World Health Conference on Periodontal Diseases 

International Sociological Association 

Scottish Health Association 

10th International Biomaterials Symposium 

International Association for the Study of Pain and Satellite 

Conference on Oral-Facial Pain 
Australian Division of the International Association of Dental 

Research 

The Institute funded six foreign research projects, one research 
fellowship, and one contract, covering the areas of craniofacial anomal- 
ies, periodontal disease, dental caries, and soft tissue stomatology. 

Within the Intramural Programs of the Institute, 44 international 
scientists were invited to present seminars on dental research topics. Six 
visiting associates, 6 visiting scientists, 15 visiting fellows, and 21 guest 
workers conducted research studies within the Bethesda laboratories of 
the Institute. 

Fluorine in Stomatology and Hygiene, a compendium of informa- 
tion for use by health professionals, was translated from Russian and 
published during the year. This 1,000-page reference volume was dis- 
tributed to selected individuals and libraries throughout the world. 

NIDR Abstracts, the quarterly publication containing summaries 
of scientific reports published by NIDR investigators, is distributed to 
approximately 150 foreign colleagues. 

In cooperation with the Smithsonian Science Information Ex- 
change, the NIDR annually publishes Dental Research in the United 
States and Other Countries. Dental scientists around the world are urged 
to register their research projects in this exchange of dental research 
information. 

The Director, NIDR, continued to serve as a member of the Oral 
Health Research Advisory Group of the Oral Health Unit, World Health 
Organization. 



117 



National Institute of Environmental Health Sciences 



Introduction 

The 12 years that NIEHS has been in existence have brought 
enormous changes in the field of environmental health. The cross- 
cutting and pervasive nature of the problems in this field have fostered 
extensive cooperation and collaboration at the international level, with 
institutions and with individual scientists. Our knowledge base has 
increased, as has awareness in the scientific and public arenas; even so, 
issues of environmental health science remain complex. 

Against this backdrop of continuing legislative, executive, and 
public interest the NIEHS carries out its mission of providing the scien- 
tific information base, advanced scientific methodol&gy, and trained 
scientific manpower to reach an understanding of the total impact of 
environmental factors on human health. International collaboration is an 
important facet of this program. 

Scientists at the NIEHS will continue to use all available avenues 
to make the world a safe place in which all peoples may work and live. 



U.S.-U.S.S.R. Cooperation 

Collaboration between Soviet and American environmental health 
scientists is carried out under the auspices of two cooperative agree- 
ments between the United States and the Soviet Union. Under the 
Medical Science and Public Health Cooperative Agreement, scientists 
from both countries are conducting joint research on heart disease, can- 
cer, arthritis, influenza and acute respiratory diseases, and on health 
problems associated with environmental pollution. The Director, NIEHS, 
is U.S. Coordinator for the environmental health activities under the 
Health Agreement. 

FY 1978 was the sixth year of formal collaboration between the 
U.S. and U.S.S.R. in environmental health research. The first year was 
concerned largely with establishing working relationships and agreeing on 
areas of joint study. Cooperative research efforts initiated in the second 
year of the agreement involved exchange visits between scientists of 
both sides. The research results developed during the second and third 
years of collaboration were presented by American and Soviet scientists 
at a joint symposium in Riga, Latvia, in December 1974. Scientific 
results from cooperative research during 1975 and 1976 were presented 
at the second joint symposium, held in Marineland, Florida, in Decem- 
ber, 1976. The results of these symposia were published in both coun- 
tries. During 1977 and 1978, major workshops were held on the topic 
"Embryotoxic and Teratogenic Effects of Chemicals" (Leningrad, No- 
vember, 1977); and "Biological Effects of Metals" (Cincinnati, February, 
1978). 



118 



Collaborative research efforts are currently divided into four 
problem areas aimed at (1) developing methods for the quantitative 
evaluation of the biological effects of environmental chemical agents; 

(2) predicting the biological effects of environmental chemical agents; 

(3) studying the long-term biological effects of environmental chemical 
agents; and (4) studying the long-term effects of physical factors in the 
environment. 

By the end of 1978, over 50 scientific papers will have been 
published by American and Soviet scientists on the results of environ- 
mental health research conducted under this agreement. 

The Agreement on Cooperation in the Field of Environmental 
Protection between the U.S. and U.S.S.R. addresses some of the most 
important aspects of problems of the environment, including the study 
of pollution and its effects on life. A number of agencies participate in 
this agreement, which is under the general direction of the Administra- 
tor, EPA. The Director, NIEHS, serves as HEW representative to the 
agreement and as co-chairman of the working group for one of its 
areas, the Biological and Genetic Effects of Pollutants. Effort in this 
area has been focused on the mutagenic potential of environmental con- 
taminants, the toxic effects of heavy metals in the environment, environ- 
mental health hazards associated with extraction, processing and 
utilization of oil from shale, the effects of environmental pollution on 
the neuroendocrine system with special emphasis on human behavioral 
effects, and the use of marine organisms to study the biological and 
genetic effects of pollutants and as models for biomedical problems. 

During 1978, program activity under this agreement consisted of 
the fourth joint workshop on "Basic and Practical Approaches to En- 
vironmental Mutagenesis and Carcinogenesis" held in Baku, U.S.S.R., 
and participation in the joint workshop on the topic "Biological Effects 
of Metals," held in Cincinnati, Ohio. In addition, exchange visits took 
place on the topics of health effects of oil shale development, human 
behavioral effects, and marine organisms. 



U.S.-Japan Cooperative Medical Sciences Program 

The Joint Panel on Environmental Mutagenesis and Carcinogenesis 
organized a Conference on Modification of Mutagenic and Carcinogenic 
Activity, which was held in October 1977. A wide range of genetic, 
biochemical, and environmental modifying factors were discussed. It was 
clear from the presentations that mutagenic response can be markedly 
modified, quantitatively as well as qualitatively. 

The Seventh Joint Conference held under this program was held 
in July 1978 at Lake Yamanaka and dealt with the Utility of Sister- 
Chromatid Exchange. A 5-year review of the work on the U.S. -Japanese 
Panel followed this workshop. 



119 



U.S.-Egypt Cooperation 

Under the auspices of the U.S.-Egypt Joint Working Group on 
Medical Cooperation, the National Institute of Environmental Health 
Sciences has been responsible for staffing and guiding the U.S. activities 
of the Subcommittee on Environmental Health. In June 1978, the U.S. 
Subcommittee visited Cairo and met with the counterpart Egyptian Sub- 
committee. At that same time the full Joint Working Group developed 
and approved a program of specific research and methodology develop- 
ment projects. 

This program has emphasized the development within Egypt of the 
capability to effectively monitor the environmental levels of known tox- 
ic agents in industrial and agricultural settings, and to assess at the 
policy level the effect of growing agricultural and industrial pollution 
within the specific ecology and environment of Egypt. 

Implementation of this program has been delayed by a reconsider- 
ation of program priorities in the light of limitations on available 
P.L.-480 funds to support research and development activities in Egypt. 
Plans for 1979 will be reevaluated by the Environmental Health Sub- 
committee, and a revised program of projects will be resubmitted to the 
Joint Working Group in June 1979. 



Collaboration With the World Health Organization 

NIEHS is a World Health Organization collaborating center for 
environmental health. NIEHS staff have been deeply involved in support 
of WHO programs. 

Specifically, staff have been involved with the preparation of a 
World Health Organization-sponsored document on "Environmental 
Health Problems Associated with the Manufacture of Synthetic Organic 
Chemicals"; participated in a meeting to help implement World Health 
Organization Assembly Resolution 30.47 on a new approach regarding 
the international evaluation of the effects of chemicals on health; and 
attended a WHO-EURO meeting dealing with the health consequences 
of chemicals occurring naturally in drinking water. In addition, one of 
our scientists served as chairman of the scientific advisory committee to 
the International Register of Potentially Toxic Chemicals of the United 
Environmental Program. 

In December 1977 Dr. Stephen Brown participated in a PAHO 
Workshop on Environmental Epidemiology in Mexico City. 

Also in December 1977, Dr. Warren Piver traveled to Geneva to 
participate in a UNEP meeting on Chemical Industry. 

During the month of October 1977 Dr. Bruce Fowler traveled to 
Stockholm, Sweden, to serve as a temporary advisor to WHO and 
participated in a meeting to review biomedical parts of the draft criteria 
document on arsenic. 



120 



Dr. Robert Dixon traveled to Buenos Aires and Santiago in July 
1978 to participate in a site visit to the South American WHO Collabor- 
ating Center for Research and Training in Human Reproduction in order 
to review their ongoing research projects and training activities. 

In June 1978 the International Agency for Research on Cancer 
convened a working group on the Evaluation of the Carcinogenic Risk 
of Chemicals to Humans to consider some halogenated hydrocarbons 
and prepare background data on specific compounds. Dr. John Moore 
was invited to come to Lyon for this meeting because of his expertise 
in this field. 

Drs. Richard Bates and Joseph Haseman traveled to Hanover, 
Germany, in May 1978 to attend the organizing committee meeting of 
the lARC Working Group to establish basic requirements for carrying 
out long-term and short-term carcinogenicity and related tests. 

The Joint lARC/NIEHS Working Group on the Coordination of 
Epidemiological Studies on the Long-term Hazards of Chlorinated 
Dihenzodioxins and Chlorinated Dihenzofurons met in Lyon, France, in 
January 1978. Dr. John Moore was the NIEHS expert at this meeting. 

Dr. David Rail traveled to Lyon, France, at the request of lARC, 
to present recommendations on the criteria for evaluating the carcino- 
genic risk of chemicals to man and to serve as a member of the panel, 
which reviewed the papers to be presented at the Symposium on Car- 
cinogenic Risks-Strategies for Intervention. 

In November Dr. Robert Dixon served as a temporary advisor to 
the Fourth Toxicology Review Panel of the WHO Special Programme of 
Research, Development, and Research Training in Human Reproduction. 

In December Dr. T.M. Ong was asked to give a presentation at a 
training course in Methods for Detection of Environmental Mutagens 
and Carcinogens for scientists in Central and South America. The meet- 
ing was held in Mexico City. 

In October the WHO Toxicology Review Panel invited Dr. E.E. 
McConnell to visit the Institute Latin American de Fisologia de la 
Reproduccion in Buenos Aires to assess the potential of that group to 
carry out programs in acute and subacute toxicology. The discussions 
centered around preclinical safety evaluations of potential therapeutic 
agents. 

Also during this month. Dr. David Hoel traveled to Lyon, France, 
to participate in a meeting of the Working Group on Criteria for Evalu- 
ating the Carcinogenic Risk of Chemicals to Man. 



Other International Collaboration 

NIEHS has a contract with the University of British Columbia, 

Vancouver, British Columbia, to assay environmental chemicals for 

mutagenic activity in a meiotic non-disjunction test in Neurospora 
crassa. 



121 



In order to develop a truly comprehensive battery of tests for 
mass screening programs, we must be able to detect all classes of genetic 
alterations. No such assay exists for non-disjunction. Because of this, we 
have only scanty evidence of chemicals which will cause non-disjunction. 
The assays with Neurospora have detected activity in 10 chemicals out 
of 62 tested. This is an important class of genetic alternation with 
regard to genetic disease in man. 

Because of the marked specificity of some chemical mutagens, it 
is considered essential to continue work with the Neurospora assay to 
evaluate its utility and feasibility as an assay system in mass screening 
programs. 

NIEHS has a grant with the State University of Leiden, Leiden, 
the Netherlands, to study induction of genetic damage by chemical 
mutagens. It is proposed to undertake a systematic study of the fre- 
quencies with which different categories of genetic damage are induced 
in a variety of different germ cell stages by representatives of both 
directly and indirectly acting mutagens under modifying conditions, 
such as storage. In addition, it is proposed to investigate in model popu- 
lations the induction of genetic damage at physiological relevant con- 
centrations after chronic application versus short-term exposure. 

NIEHS supports a grant at the University of Western Ontario, 
London, Canada, to study the nature of lead and mercury binding 
nuclear proteins. The major objectives of the study are to determine the 
nature of proteins forming intracellular complexes with potentially toxic 
metals (lead and mercury), the functional changes in the cell containing 
intranuclear inclusions and the effect of chelating agents in tissue culture 
to remove the metal. These metals are known to bind intracellularly 
with acidic nuclear proteins, but it is not known whether these proteins 
are synthesized specifically for binding with these metals. 

Another grant with the University of Turku, Turku, Finland, has 
investigators studying gastrointestinal and pulmonary metabolic func- 
tions. It is well accepted that the gastrointestinal tract actively partici- 
pates in foreign substance metabolism. Recently similar activities have 
been demonstrated in pulmonary tissue. Further exploration of these 
functions is planned. Further identification of the biochemical machin- 
ery carrying out these numerous functions will be attempted. In addi- 
tion, adaptation of these functions on subcellular levels under various 
experimental conditions will be studied. 

NIEHS supports a grant to TelAviv University, Ramat Aviv, Israel, 
to study hydrocarbon recognition in petroleum-degrading bacteria. 
Research is being carried out on the transport of water-immiscible and 
water-soluble petroleum hydrocarbons by microorganisms. Emphasis is 
on characterization of bacterial emulsifying agents and their role in 
hydrocarbon movement from the medium to the cell surface and across 
the cell membrane. 

Dr. LP. Lee and scientists from the Institute of Toxicology and 
the University of Zurich are collaborating on developing a new method 
for accurately identifying mutagens and carcinogens through an in vivo 
animal model. 



122 



The MRC/ICI/NIEHS internaional trial to test paired compounds 
consisting of chemical carcinogens and noncarcinogenic structural ana- 
logs as well as selected chemicals to serve as positive and negative con- 
trols has been continued. This study has been developed in cooperation 
with the Medical Research Council and the Imperial Chemical Industries 
in Great Britain, the International Association of Environmental Muta- 
gen Societies and NIEHS. The study will involve collaboration between 
50 scientists in different laboratories all over the world who will com- 
pare various assays for mutagenicity in blind tests on about 42 
compounds. 

A collaborative study on the effects of inhaled asbestos was begun 
with the Pneumonoconiosis Research Unit, Medical Research Council, 
United Kingdom. Using an agreed upon protocol, we are studying the 
respiratory effects of various types of fibers which may be present in 
either the working environment or the rest of our environment. Major 
concentration is on asbestos but we are also looking at glasswool and 
rockwool. 

Collaborative research between the Transplacental Toxicology 
Workgroup at NIEHS and Dr. Manfred Metzler, Institute for Pharmacol- 
ogy and Toxicology, University of Wurzburg, Wurzburg, West Germany, 
includes studies on the target organ metabolism and bioactivation of the 
carcinogenic estrogen, diethylstilbestrol (DES). These studies involve 
whole animal experiments and tissue culture systems as well as studies 
on the in vitro binding of DES or its metabolites to intracellular and 
extracellular receptor proteins. Such studies should provide new insights 
into mechanisms of hormonal carcinogenesis. 

Collaborative work on the effect of hormones and hormonally 
active xenobiotics on the control of blood coagulation in the rat has 
been and is now being done with Dr. Etsuko Kita, Department of 
Clinico-Laboratory Diagnostics, Nara Medical College, Nara, Japan, and 
Dr. Coral Lamartiniere of NIEHS. In addition, Dr. Kita was a guest 
worker in Dr. Lamartiniere's lab during the period May 1977 to May 
1978. 

During the past year we have continued to support the Environ- 
mental Mutagen Information Center by interagency agreement at the 
Oak Ridge National Laboratory. The Center continues to work closely 
with investigators around the world in both obtaining and supplying 
information on the aibject of environmental mutagenesis. The Center 
has over 25,000 bibliographic entries in its data banks and continues 
as a unique worldwide resource for information in the area of environ- 
mental chemical mutagenesis. 

Communication of basic and applied information vital to environ- 
mental health problems is aided by establishing mechanisms for informa- 
tion exchange. In this regard, NIEHS has established the much-needed 
Environmental Teratology Information Center in collaboration with the 
Department of Energy and the Oak Ridge National Laboratories. Infor- 
mation on teratology is collected, indexed and made available to the 
biomedical community directly from the Center or the National Library 



123 



of Medicine's TOXLINE. ETIC is a unique worldwide resource for 
information in the area of teratology. 

Professor F, Pocchiari and Dr. L. Giannico, Ministry of Health, 
Rome, met with NIEHS scientists to discuss "Health Aspects of En- 
vironmental Pollution." The following areas were agreed upon for 
cooperation: 

A. Evaluation of chemicals for possible human toxicity 

1. Chemical selection 

2. Test methodology 

3. Extrapolation of results from laboratory animals to 
human populations 

4. Assessment of risks to the human population 

B. Understanding the mechanism of action of environmental 
chemicals with possible human toxicity 

C. Surveillance and epidemiological assessment of the effects of 
environmental chemicals in human and nonhuman populations 



National Institute of Neurological and Communicative 
Disorders and Stroke 



Introduction 

The National Institute of Neurological and Communicative Dis- 
orders and Stroke (NINCDS) serves as the NIH focal point for research 
on the basic and clinical aspects of the nervous system and human com- 
munication. Through its research grant program, participation in the 
Special Foreign Currency Program and collaborative research efforts 
between NINCDS scientists and their foreign colleagues, the Institute 
maintains a continuing interaction with neurological and communicative 
scientists internationally. 

In addition, since 1975 the NINCDS has been one of eight WHO 
Collaborating Centers in the Neurosciences. These centers, positioned 
strategically throughout the world, further international research efforts 
on neurological disorders, and initiate and demonstrate community 
programs for the prevention and treatment of such disorders. At this 
time, special emphasis is being given to the cerebrovascular disorders 
(stroke) and the convulsive disorders (epilepsy). 

As part of this effort, the NINCDS, the Fogarty International 
Center, and WHO jointly sponsor a Neuroscience Fellowship Program. 
This program provides men and women from developing countries with 
stipend support for advanced training in the United States, to prepare 
them for academic and public health careers in their own countries. 



124 



Foreign Research Grants 

NINCDS supported 13 foreign research projects in FY 1978, 
totaling $1,082,905. Four of these projects were in Canada; three in 
Israel; two in Sweden; two in Mexico; one in Italy; and one in New 
Zealand. These grants represent both clinical and basic research, and 
have been awarded to outstanding investigators exploring problems of 
high priority to the United States and their own countries. The largest 
award is to Henry J. Barnett of the University of Western Ontario 
($645,811) for an international multi-institutional cooperative study 
evaluating the efficacy of extracranial/intracranial arterial anastomosis. 

Foreign NINCDS research grants complement those made to U.S. 
investigators in that they are expected to provide information not being 
adequately developed in this country. In some cases opportunities are 
unique to the country involved; in all cases the workers are outstanding 
and their contributions will help American scientific efforts. They are an 
important aspect of international health cooperation; they place NIH 
financial and intellectual resources in contact with the skills, opportuni- 
ties, and resources available in other countries. The entire process of 
accumulation of knowledge in the neurosciences is thus materially 
enhanced. 



Special Foreign Currency Program (P.L.-480) Grants 

NINCDS currently sponsors 11 P.L.-480 projects: three in Egypt; 
one in India; three in Poland, and four in Yugoslavia. FY 1978 funding 
was for the three projects in Egypt, totaling $338,691. These were a 
project for perinatal screening of developmental malformations, and two 
studies of the biochemistry and enzymology of poisonous snake venoms 
affecting the nervous system. 

P.L.-480 grants are a small but important segment of the NINCDS- 
NIH research support program in that they provide information not 
being adequately developed here. In some cases, opportunities are 
unique to the country involved; in others, special economies are possible 
through this program. In all cases the investigators are outstanding and 
their contributions will help to advance the world's knowledge in the 
neurosciences. 



WHO Collaborating Centers for Research 
and Training in the Neurosciences 

NINCDS is one of eight WHO Collaborating Centers for Research 
and Training in the Neurosciences. The others are: 



125 



The Institute Nacional de Neurologica; Mexico City, Mexico 
The Montreal Neurological Institute; Montreal, Canada 
The Groupe Hospitaller de la Timone, Marseilles, France 
The Centre National de la Recherche Scientifique; Strasbourg, 

France 
The University of Geneva; Geneva, Switzerland 
The University of Ibaban; Ibaban, Nigeria 
The Academy of Medical Sciences of the U.S.S.R.; Moscow, 

U.S.S.R. 

Each center funds its own activities, which consist of collaborative 
research, publications for scientific information exchange, support of 
conferences and courses, advisory services, and training. In FY 1978, 
Drs. Donald B. Tower and Murray Goldstein of NINCDS presented 
lectures as part of a Collaborating Centers Program-sponsored training 
course in cerebrovascular disorders and stroke in Lima, Peru. 

In FY 1978, NINCDS funding for this activity was limited to pro- 
gram travel expenses. Funds have been set aside to support international 
research fellowships in 1979 in the amount of $100,000. 

This program meshes with the broader commitments of NIH for 
international health cooperation. Opportunities for neuroscience col- 
laboration and interchange with scientists in other countries are virtually 
unlimited. Stroke epidemiology is a good example of an area where 
great mutual benefits are possible, as there are known to be wide vari- 
ations in stroke mortality, incidence, and age groups affected in differ- 
ent parts of the world. 

The principal aspect of this program, in relation to international 
health cooperation, is that it brings together the world's experts in the 
various neuroscience areas so that their combined knowledge is brought 
to bear on problems common to all countries. 

This program was begun in 1974 with five centers, and has since 
been expanded to eight. Major emphasis is now on stroke and epilepsy, 
two problems severely affecting health in every country of the world. 
In terms of time, the program is ongoing, and will continue as funds and 
staff resources permit. 

The trend in NINCDS foreign research grants has been downward 
because of the increased competition for funds and the leveling off of 
appropriations in real dollar terms. The Institute hopes to maintain the 
level of funding for these grants, but this will depend upon future eco- 
nomic and budget factors. 

The trend in P.L.-480 research grants has been downward, because 
of decreased availability of counterpart funds in the countries where 
neuroscience research can be conducted. 

Interest in the Collaborating Centers Program is growing, and 
activities are steadily increasing. The Institute hopes to be able to con- 
tinue to cooperate and contribute as it has in the past. 



126 



National Library of Medicine 



The National Library of Medicine (NLM) is a national resource 
with international impact. Its international activities include: bilateral 
quid proquo MEDLARS agreements; exchange of biomedical literature; 
collaboration with national and international organizations in their 
establishment of regional services; information services to the developing 
countries through an NLM/Agency for International Development (AID) 
agreement; special foreign currency program for the support of publica- 
tions; participation in international organizations; providing technical 
consultation; and receiving non-U.S. colleagues for specialized training. 



International MEDLARS Agreements 

NLM has 11 international MEDLARS partners; Australia, Canada, 
France, Germany, Iran, Japan, Mexico, South Africa, Sweden, United 
Kingdom, and the Pan American Health Organization (PAHO). Policy 
officials and directors of the foreign MEDLARS centers attended the 
Fifth Meeting of the International MEDLARS Policy Advisory Group 
October 27-28, 1977. This meeting provided an opportunity for joint 
review of policies, experiences and future plans of NLM and the centers. 

At the meeting, issue papers were presented on document delivery 
by Sir Harry Hookway and Dr. Philip Holmes of the United Kingdom; 
data base building by Dr. Henry Kissman, NLM associate director for 
Specialized Information Services; and networking by Dr. S. Abrahamsson 
and Dr. Goran Falkenberg of Stockholm, Sweden. 

Of particular interest were the regional activities of the Pan Amer- 
ican Health Organization's Regional Library of Medicine (BIREME) and 
the Pahlavi Library of Medicine in Iran which was designated in 1978 as 
the WHO Regional Library for the eastern Mediterranean. One principal 
concern of the policy group was how to provide services to the develop- 
ing countries now that WHO has terminated its MEDLINE activities. 
Most of the centers are faced with limitations on personnel, and exten- 
sive free services to the developing countries could be undertaken only if 
sponsored and funded by the appropriate technical assistance or develop- 
ment agency within the providing countries. 

The quid pro quo bilateral agreement, which is the basis for inter- 
national MEDLARS collaboration, continues as an effective mechanism 
for cooperation. Together, these bilateral arrangements constitute essen- 
tially an international network in which the value of biomedical in- 
formation is recognized as vital to the advancement of medical research, 
education, and the improvement of health. Table 1 summarizes the 
modes of access to the NLM data bases. Ten data bases— MEDLINE, 
TOXLINE, CHEMLINE, CATLINE, SERLINE, AVLINE, CANCERLIT, 
CANCERPROJ, CLINPROT, RTECS-are available to the foreign cen- 
ters, but not all centers have chosen to search all data bases. 



127 



Table 1. International Access to MEDLARS 



Tapes 

Germany 
Japan 



+ Supplemental online access to NLM computer 



Tapes/Software 


Online NLM 


Sweden 


France 


United Kingdom 


Canada 


Australia 


Iran 


PAHO 


Mexico 




South Africa 



International Exchanges and Services 

The NLM continues its international publications exchange pro- 
gram with 810 institutions in 87 countries where an equitable exchange 
balance can be achieved. This program is in addition to NLM's regular 
acquisitions program and often provides both NLM and the participating 
country with material not easily obtained otherwise. 

In FY 1978 the assistant director for International Programs was 
invited to visit Cuba by the Minister of Public Health to observe Cuba's 
health information activities. As a result of this visit, a cooperative 
program was established in the exchange of publications between the 
National Information Center for Medical Sciences of the Ministry of 
Health in Cuba and NLM. The Library also accepted for special training 
Pompeya Garcia, director of the National Medical Library of Cuba and 
Diasy de Valle, director. Department of Information Development of the 
National Information Center for Medical Sciences. 

The NLM provides interlibrary loans of published and audiovisual 
materials internationally for a fee. Exceptions have been made for coun- 
tries with which the United States Agency for International Develop- 
ment has a health program. Under an agreement between AID and NLM, 
the Library has provided during the past year approximately 22,000 
interlibrary loans, 12 reference replies, 497 MEDLINE searches, 52 sub- 
scriptions to Index Medicus and 48 subscriptions to Abridged Index 
Medicus. Approximately 25 percent of these were for technical support 
of PAHO's Regional Library of Medicine in Sao Paulo, Brazil; 36 per- 
cent to Turkey; 10 percent to India; 9 percent to Indonesia; and 7 
percent to Korea. This agreement terminates at the end of FY 1978. 
Future international interlibrary loan of documents and loan of audio- 
visual material will be on a fee for services basis only. 



Special Foreign Currency Program ^'^'"'^ 

The Library's Special Foreign Currency Program, authorized by 
Public Law 83-480, made 20 new awards in FY 1978 for a total of 88 



128 



active projects for $1,680,423 (equivalent). Under the NLM SFC pro- 
gram, appropriations of U.S. -owned, local foreign currencies are utilized 
for scientific writing projects in cooperating countries, including Poland, 
Tunisia, India, Pakistan, Egypt, and Yugoslavia. The collaborative NLM 
program also is continued in Israel through a bloc award from the 
U.S. -Israel Binational Science Foundation. 

Included among the projects in the seven cooperating countries 
are the preparation of critical reviews and monographs analyzing bio- 
medical research and practice; translations of foreign monographs in the 
health sciences; studies in the history of medicine; the publication of 
major international symposia and conference proceedings; and the 
preparation and publication of authoritative bibliographies, guides, and 
other literature tools in the biomedical sciences. The program makes it 
possible for the Library to procure and disseminate published informa- 
tion which is important to the progress of the biomedical sciences and 
the public health, using foreign scientific personnel and resources. 

Critical reviews and biomedical monographs continue to be the 
most frequent type of project undertaken in the program, constituting 
66 percent of the funding. Fifty-five percent of all projects active in 
FY 1978 were undertaken in two countries— Poland and Israel. During 
FY 1978 Dr. Saul Jarcho, consultant to the NLM Board of Regents, 
accompanied by Dr. Jeanne Brand, chief of NLM's International Pro- 
grams Division, carried out a program review of the Library's publication 
activities in Egypt. Among other projects currently being developed in 
that country are a series of studies in the history of Arabic medicine. 

Examples of new projects activated in FY 1978 include a critical 
review on surgery of the spleen, a translation of a Russian study of 
emotional stress and arterial hypertension, and a catalogue of manu- 
scripts on medicine and pharmacy in the National Library of Cairo and 
the Municipal Library of Alexandria, Egypt. 

, Among the books published in FY 1978 under this program was 
Early Therapeutic, Social and Vocational Problems in the Rehabilitation 
of Persons with Spinal Cord Injuries (New York: Plenum Press, 1977), 
edited by Professor Marian Weiss, director of the internationally recog- 
nized Rehabilitation Clinic at Konstancin, Poland. Another significant 
study, funded in the NLM program in Israel, reviews current develop- 
ments in family medical practice— Jack H. Medalie, editor. Family 
Medicine-Principles and Applications (Baltimore: The Williams and 
Wilkins Co., 1978). 



Regional Resources and Biomedical Information 

The PAHO Regional Library of Medicine (BIREME) continues as 
a model activity in serving as a regional biomedical and health informa- 
tion resource. Its extensive activities include exchange of materials. 



129 



reference services, interlibrary loans, computer-based information services 
from the MEDLARS data base and developing a library network. 

About 16 percent of BIREME's annual budget is provided by 
PAHO's regular budget, 7 percent from WHO, and 77 percent from 
external sources including federal, state, and local governments of Brazil, 
and from philanthropic agencies. The staff of the Library has increased 
from 23 in 1969 to 71 in 1978. The most significant aspect of this 
increase is the addition of physicians and especially trained professional 
personnel. Since 1969, BIREME has performed 288,000 loan services; 
prepared 8,255 special bibliographies; and obtained and donated 
309,000 journal issues to other Latin American libraries to strengthen 
their collections; and has provided specialized training to 324 Latin 
librarians. 

Dr. Cummings, Director of NLM and chairman of the scientific 
advisory committee for BIREME, attended the tenth meeting of the 
committee in Sao Paulo, Brazil. The committee reviewed both policy 
considerations and the operational status of BIREME. 

The Pahlavi Library of Medicine, established in Tehran, Iran, in 
1975, has recruited and trained additional staff. It has also initiated an 
audiovisual program to assist the health community and has increased 
its specialized staff. In January 1978 the World Health Organization 
(WHO) designated the Pahlavi Library of Medicine as a WHO Regional 
Center for providing biomedical information services to the WHO eastern 
Mediterranean region. 

Cooperation is being initiated between the World Health Organiza- 
tion's advisory committee on medical research and the National Library 
of Medicine. The National Library of Medicine will produce a specialized 
recurring bibliography in those tropical diseases selected by WHO for 
primary emphasis. The Pahlavi Library of Medicine will print it and the 
WHO will distribute approximately 10,000 copies. This model activity, 
when tested, may serve as a basis for developing further specialized 
information services and products significant for developing countries. 



Visitors and Specialized Training 

NLM receives about 1,000 international visitors annually. During 
FY 1978 these individuals represented 49 countries and many interests, 
such as medical research and education, health care, information and 
library science, administration and development of biomedical and 
health information programs, and construction of new library buildings. 

Formal delegations from Japan included representatives of the 
Ministry of Health and Welfare, the Diet Library, and computer and 
information organizations. Groups of librarians came from Brazil, Spain, 
Germany and Colombia. Delegations from Italy were from the Ministry 
of Health and the National Federation of Medicine, which included the 
Chief of the Cabinet of the Ministry of Health, members of the Italian 



130 



Parliament, and physicians. Australian visitors have included Senator 
Davidson; Mr. K.W. Edmondson, secretary of the National Health and 
Medical Research Council; Mr. J.G. Burt, the assistant director general. 
Department of Health; Dr. G.N. Lance, the chief research scientist. 
Commonwealth Scientific and Industrial Research Organization; and, 
from the National Library of Australia, Mr. Bryan Yates, the deputy 
director; Mr. A. Ellis, the assistant director general for Networks and 
Coordination; and Mr. T. Barley, the chief of computer systems. 

NLM also assists other agencies in receiving and preparing pro- 
grams for information specialists from other countries. 

In connection with NLM's bilateral MEDLARS agreements, NLM 
has received a number of individuals for specialized programs. They 
include: George Milligan of the Institute for Medical Literature, South 
African Medical Research Council, for training in indexing medical 
literature and searching the various NLM data bases; Fahimeh Shafaie 
of the Pahlavi Library of Medicine in Iran for training in audiovisuals; 
Dr. Cesar Macias of the National Center for Information and Documen- 
tation in Health of the Ministry of Health, Mexico, for advanced training 
as a search analyst; and Caterina Vollono of the Istituto Superiore di 
Sanita in Rome, Italy, for training in searching the various NLM data 
bases. 

The NLM does not have, nor does it fund, a formal program for 
trainees from abroad. It does, however, try to respond to special re- 
quests from other governments or institutions where a person's experi- 
ence qualifies him for specialized training which can be applied upon his 
return home. Some of those in such programs were: Pompeye Garcia, 
director of the National Medical Library in Cuba; Daisy de Valle, direc- 
tor of the department of information development of the National 
Information Center for Medical Sciences, Ministry of Public Health, 
Cuba; Dr.med. Oystein Wendelbo, deputy librarian. University Library 
of Bergen, Norway; and Dr. Reinhard Bradler from the German State 
Library, Berlin, East Germany. 

In June, Miss Mary E. Corning, NLM, served as a consultant to 
the Subcommittee on Health Manpower and Medical Education of the 
U.S. -Egyptian Working Group on Health during the latter's meetings in 
Egypt. She also reviewed with the World Health Organization Regional 
Office in Alexandria the Egyptian medical library scene, WHO's designa- 
tion of the Pahlavi Library of Medicine in Iran as a WHO Regional 
Library, WHO's plans for developing a medical library network in the 
region, and WHO's planned health information system. 



us GOVtRNMENT PRINTING OFFICE 1979-281-217/3244 



131 



■-.ii'^i'uMQs, 



DATE DUE 


















































































































































CAYLORD 




PRIMTCO IN U.S.A. 



NIH LIBRARY 

liilll